Charakterystyka i zastosowanie kliniczne dydrogesteronu – Stanowisko Grupy Ekspertów Stanowisko ekspertów
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Opublikowane:
gru 31, 2023
Słowa kluczowe:
dydrogesteron, progestageny, ciąża, wsparcie fazy lutealnej, hormonalna terapia menopauzalna, zaburzenia miesiączkowania
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Abstrakt
Dydrogesteron został wprowadzony na rynek w 1961 r. i obecnie jest dostępny w ponad 100 krajach na całym świecie. Charakteryzuje się on dobrą biodostępnością i stabilnością metaboliczną, a także brakiem właściwości estrogenowych, androgenowych oraz mineralokortykoidowych i dobrym profilem bezpieczeństwa, dzięki czemu w wielu przypadkach klinicznych stanowi dobrą alternatywę dla innych progestagenów. Znajduje on zastosowanie w licznych wskazaniach ginekologiczno-położniczych, w tym w zaburzeniach wpływających na miesiączkę i ciążę, oraz w hormonalnej terapii menopauzalnej.
W niniejszym dokumencie przedstawiono stanowisko Grupy Ekspertów na temat możliwości stosowania dydrogesteronu w praktyce klinicznej. Przeprowadzono narracyjny przegląd bazy literaturowej, skupiając się na kwestii skuteczności i bezpieczeństwa dydrogesteronu stosowanego w: nieprawidłowych krwawieniach z macicy, bolesnym miesiączkowaniu, zespole napięcia przedmiesiączkowego, wtórnym braku miesiączki, leczeniu poronienia zagrażającego i nawracającego, niepłodności związanej z niewydolnością ciałka żółtego, endometriozie oraz w hormonalnej terapii menopauzalnej.
Zidentyfikowane dowody naukowe potwierdzają, że stosowanie dydrogesteronu w wielu sytuacjach klinicznych może być korzystne, a profil bezpieczeństwa leku jest bardzo dobry. Szerokie wykorzystanie dydrogesteronu w praktyce ginekologiczno-położniczej niewątpliwie jest zasadne, choć niezbędne są dalsze badania randomizowane, które bezsprzecznie potwierdzą skuteczność leku we wszystkich wskazaniach.
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Jak cytować
Kwiatkowski, S., Sieroszewski, P., Kalinka, J., Paszkowski, T., Kuczyński, W., Jakimiuk, A., Skrzypulec-Plinta, V., Wender-Ożegowska, E., Pawelczyk, L., & Huras, H. (2023). Charakterystyka i zastosowanie kliniczne dydrogesteronu – Stanowisko Grupy Ekspertów. Medycyna Faktów , 16(4(61), 295-302. https://doi.org/10.24292/01.MF.0423.0X
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Artykuły
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Bibliografia
1. Queisser-Luft A. Dydrogesterone use during pregnancy: Overview of birth defects reported since 1977. Early Human Development. 2009; 85(6): 375-7.
2. Charakterystyka produktu leczniczego Duphaston (dydrogesteron).
3. Charakterystyka produktu leczniczego Femoston (Estradiol+dydrogesteron).
4. Charakterystyka produktu leczniczego Femoston mite (Estradiol+dydrogesteron).
5. Charakterystyka produktu leczniczego Femoston conti (Estradiol+dydrogesteron).
6. Charakterystyka produktu leczniczego Femoston mini (Estradiol+dydrogesteron).
7. Schindler AE. Differential effects of progestins: European Progestin Club. Maturitas. 2003; 46: 3-5.
8. Griesinger G, Tournaye H, Macklon N et al. Dydrogesterone: pharmacological profile and mechanism of action as luteal phase support in assisted reproduction. Reprod Biomed Online. 2019; 38(2): 249-59.
9. Schindler AE. Progestational effects of dydrogesterone in vitro, in vivo and on the human endometrium. Maturitas. 2009; 65(suppl 1): S3-11.
10. Qing G, Hong Y, Feng X et al. Comparison of oral dydrogesterone and intramascular progesterone in the treatment of threatened abortion. Biomedica. 2015; 31(3): 223-7.
11. Foster RH, Balfour JA. Estradiol and dydrogesterone. A review of their combined use as hormone replacement therapy in postmenopausal women. Drugs Aging. 1997; 11(4): 309-32.
12. Rižner TL, Brožič P, Doucette C et al. Selectivity and potency of the retroprogesterone dydrogesterone in vitro. Steroids. 2011; 76(6): 607-15.
13. Griesinger G, Blockeel C, Tournaye H. Oral dydrogesterone for luteal phase support in fresh in vitro fertilization cycles: a new standard? Fertil Steril. 2018; 109(5): 756-62.
14. Tournaye H, Sukhikh GT, Kahler E et al. A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization. Hum Reprod. 2017; 32(5): 1019-27.
15. Whitaker L, Critchley HOD. Abnormal uterine bleeding. Best Pract Res Clin Obstet Gynaecol. 2016; 34: 54-65.
16. Wang L, Guan H-Y, Xia H-X et al. Dydrogesterone treatment for menstrual-cycle regularization in abnormal uterine bleeding – ovulation dysfunction patients. World J Clin Cases. 2020; 8(15): 3259-66.
17. Trivedi N, Chauhan N, Vaidya V. Effectiveness and safety of dydrogesterone in regularization of menstrual cycle: a post-marketing study. Gynecol Endocrinol. 2016; 32(8): 667-71.
18. Guimarães I, Póvoa AM. Primary Dysmenorrhea: Assessment and Treatment. Rev Bras Ginecol Obstet. 2020; 42(8): 501-7.
19. Stute P. Dydrogesterone indications beyond menopausal hormone therapy: an evidence review and woman’s journey. Gynecol Endocrinol. 2021; 37(8): 683-8.
20. Taniguchi F, Ota I, Iba Y et al. The efficacy and safety of dydrogesterone for treatment of dysmenorrhea: An open-label multicenter clinical study. J Obstet Gynaecol Res. 2019; 45(1): 168-75.
21. Aydar CK, Coleman BD. Treatment of Primary Dysmenorrhea: A Double-Blind Study. JAMA. 1965; 192(11): 1003-5.
22. Gould CH. Dydrogesterone in teenage dysmenorrhoea. A multicentre trial in general practice. Practitioner. 1979; 222(1331): 718-23.
23. Tiranini L, Nappi RE. Recent advances in understanding/management of premenstrual dysphoric disorder/premenstrual syndrome. Fac Rev. 2022; 11: 11.
24. Khajehei M, Abdali K, Parsanezhad ME et al. Effect of treatment with dydrogesterone or calcium plus vitamin D on the severity of premenstrual syndrome. Int J Gynaecol Obstet. 2009; 105(2): 158-61.
25. Kerr GD, Day JB, Munday MR et al. Dydrogesterone in the treatment of the premenstrual syndrome. Practitioner. 1980; 224(1346): 852-5.
26. Panay N, Pritsch M, Alt J. Cyclical dydrogesterone in secondary amenorrhea: results of a double-blind, placebo-controlled, randomized study. Gynecol Endocrinol. 2007; 23(11): 611-8.
27. Hadaś K, Warenik-Szymankiewicz A, Halerz-Nowakowska B et al. [Repeated amenorrhea after body weight loss. Efficacy of treatment of estrogen and gestagen depending on the body mass index]. Ginekol Pol. 1999; 70(5): 383-8.
28. Battino S, Ben-Ami M, Geslevich Y et al. Factors associated with withdrawal bleeding after administration of oral dydrogesterone or medroxyprogesterone acetate in women with secondary amenorrhea. Gynecol Obstet Invest. 1996; 42(2): 113-6.
29. Katalinic A, Shulman LP, Strauss JF et al. A critical appraisal of safety data on dydrogesterone for the support of early pregnancy: a scoping review and meta-analysis. Reprod Biomed Online. 2022; 45(2): 365-73.
30. Walch K, Hefler L, Nagele F. Oral dydrogesterone treatment during the first trimester of pregnancy: the prevention of miscarriage study (PROMIS). A double-blind, prospectively randomized, placebo-controlled, parallel group trial. J Matern Fetal Neonatal Med. 2005; 18(4): 265-9.
31. Carp H. A systematic review of dydrogesterone for the treatment of recurrent miscarriage. Gynecol Endocrinol. 2015; 31(6): 422-30.
32. The ESHRE Guideline Group on RPL; Bender Atik R, Christiansen OB, Elson J et al. (2023) ESHRE guideline: recurrent pregnancy loss: an update in 2022. Hum Reprod Open. 2023(1): hoad002.
33. Wahabi HA, Fayed AA, Esmaeil SA et al. Progestogen for treating threatened miscarriage. Cochrane Database Syst Rev. 2018(8): CD005943.
34. Czajkowski K, Sienko J, Mogilinski M et al. Uteroplacental circulation in early pregnancy complicated by threatened abortion supplemented with vaginal micronized progesterone or oral dydrogesterone. Fertil Steril. 2007; 87(3): 613-8.
35. Das R, Rout RR, Tiwari RVC et al. Evaluation of per Vaginal Bleeding With Different Drugs in Successful Pregnancy in Patients With Recurrent Pregnancy Loss: An Original Research. J Pharm Bioallied Sci. 2022; 14(suppl 1): S193-5.
36. Ghosh S, Chattopadhyay R, Goswami S et al. Assessment of sub-endometrial blood flow parameters following dydrogesterone and micronized vaginal progesterone administration in women with idiopathic recurrent miscarriage: a pilot study. J Obstet Gynaecol Res. 2014; 40(7): 1871-6.
37. Kale AR, Kale AA, Yelikar K. A Comparative, Randomized Control Trial in Patients of Per Vaginal Bleeding Comparing Efficacy of Oral Dydrogesterone Versus Vaginal Progesterone in Successful Pregnancy Outcome for Patients with Recurrent Pregnancy Loss. J Obstet Gynecol India. 2021; 71(6): 591-5.
38. Kalinka J, Szekeres-Bartho J. The impact of dydrogesterone supplementation on hormonal profile and progesterone-induced blocking factor concentrations in women with threatened abortion. Am J Reprod Immunol. 2005; 53(4): 166-71.
39. Ott J, Egarter C, Aguilera A. Dydrogesterone after 60 years: a glance at the safety profile. Gynecol Endocrinol. 2022; 38(4): 279-87.
40. van der Linden M, Buckingham K, Farquhar C et al. Luteal phase support for assisted reproduction cycles. Cochrane Database Syst Rev. 2015; (7): CD009154.
41. Balasch J, Vanrell JA, Márquez M et al. Dehydrogesterone versus vaginal progesterone in the treatment of the endometrial luteal phase deficiency. Fertil Steril. 1982; 37(6): 751-4.
42. Fatemi HM, Popovic-Todorovic B, Papanikolaou E et al. An update of luteal phase support in stimulated IVF cycles. Hum Reprod Update. 2007; 13(6): 581-90.
43. Orazov MR, Radzinskiy VE, Nosenko EN et al. Combination therapeutic options in the treatment of the luteal phase deficiency. Gynecol Endocrinol. 2017; 33(suppl 1): 1-4.
44. Koninckx PR, Fernandes R, Ussia A et al. Pathogenesis Based Diagnosis and Treatment of Endometriosis. Front Endocrinol (Lausanne). 2021; 12: 745548.
45. Peng C, Huang Y, Zhou Y. Dydrogesterone in the treatment of endometriosis: evidence mapping and meta-analysis. Arch Gynecol Obstet. 2021; 304(1): 231-52.
46. Sun S, Zhang H, Zhong P et al. The Effect of Letrozole Combined with Dydrogesterone for Endometriosis in China: A Meta-Analysis. Biomed Res Int. 2021; 2021: 9946060.
47. Sukhikh GT, Adamyan LV, Dubrovina SOet al. Prolonged cyclical and continuous regimens of dydrogesterone are effective for reducing chronic pelvic pain in women with endometriosis: results of the ORCHIDEA study. Fertil Steril. 2021; 116(6): 1568-77.
48. de Carvalho BR. Dydrogesterone as an Option in the Medical Treatment of Endometriosis: A Brief Comment. Rev Bras Ginecol Obstet. 2022; 44(8): 802-3.
49. Stevenson JC, Durand G, Kahler E et al. Oral ultra-low dose continuous combined hormone replacement therapy with 0.5 mg 17β-oestradiol and 2.5 mg dydrogesterone for the treatment of vasomotor symptoms: results from a double-blind, controlled study. Maturitas. 2010; 67(3): 227-32.
50. Ren M, Ruan X, Gu L et al. Ultra-low-dose estradiol and dydrogesterone: a phase III study for vasomotor symptoms in China. Climacteric. 2022; 25(3): 286-92.
51. Nieto JJ, Cogswell D, Jesinger D et al. Lipid effects of hormone replacement therapy with sequential transdermal 17-beta-estradiol and oral dydrogesterone. Obstet Gynecol. 2000; 95(1): 111-4.
52. Kuba VM, Teixeira MA, Meirelles RMR et al. Dydrogesterone does not reverse the cardiovascular benefits of percutaneous estradiol. Climacteric. 2013; 16(1): 54-61.
53. Piróg M, Jach R, Kacalska-Janssen O. Differential effect of the ultra-low dose and standard estrogen plus dydrogesterone therapy on thrombin generation and fibrinolysis in postmenopausal women. Acta Obstet Gynecol Scand. 2017; 96(12): 1438-45.
54. Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases. BMJ. 2020; 371: m3873.
55. Fournier A, Mesrine S, Dossus L et al. Risk of breast cancer after stopping menopausal hormone therapy in the E3N cohort. Breast Cancer Res Treat. 2014; 145(2): 535-43.
56. Fournier A, Dossus L, Mesrine S et al. Risks of endometrial cancer associated with different hormone replacement therapies in the E3N cohort, 1992-2008. Am J Epidemiol. 2014; 180(5): 508-17.
2. Charakterystyka produktu leczniczego Duphaston (dydrogesteron).
3. Charakterystyka produktu leczniczego Femoston (Estradiol+dydrogesteron).
4. Charakterystyka produktu leczniczego Femoston mite (Estradiol+dydrogesteron).
5. Charakterystyka produktu leczniczego Femoston conti (Estradiol+dydrogesteron).
6. Charakterystyka produktu leczniczego Femoston mini (Estradiol+dydrogesteron).
7. Schindler AE. Differential effects of progestins: European Progestin Club. Maturitas. 2003; 46: 3-5.
8. Griesinger G, Tournaye H, Macklon N et al. Dydrogesterone: pharmacological profile and mechanism of action as luteal phase support in assisted reproduction. Reprod Biomed Online. 2019; 38(2): 249-59.
9. Schindler AE. Progestational effects of dydrogesterone in vitro, in vivo and on the human endometrium. Maturitas. 2009; 65(suppl 1): S3-11.
10. Qing G, Hong Y, Feng X et al. Comparison of oral dydrogesterone and intramascular progesterone in the treatment of threatened abortion. Biomedica. 2015; 31(3): 223-7.
11. Foster RH, Balfour JA. Estradiol and dydrogesterone. A review of their combined use as hormone replacement therapy in postmenopausal women. Drugs Aging. 1997; 11(4): 309-32.
12. Rižner TL, Brožič P, Doucette C et al. Selectivity and potency of the retroprogesterone dydrogesterone in vitro. Steroids. 2011; 76(6): 607-15.
13. Griesinger G, Blockeel C, Tournaye H. Oral dydrogesterone for luteal phase support in fresh in vitro fertilization cycles: a new standard? Fertil Steril. 2018; 109(5): 756-62.
14. Tournaye H, Sukhikh GT, Kahler E et al. A Phase III randomized controlled trial comparing the efficacy, safety and tolerability of oral dydrogesterone versus micronized vaginal progesterone for luteal support in in vitro fertilization. Hum Reprod. 2017; 32(5): 1019-27.
15. Whitaker L, Critchley HOD. Abnormal uterine bleeding. Best Pract Res Clin Obstet Gynaecol. 2016; 34: 54-65.
16. Wang L, Guan H-Y, Xia H-X et al. Dydrogesterone treatment for menstrual-cycle regularization in abnormal uterine bleeding – ovulation dysfunction patients. World J Clin Cases. 2020; 8(15): 3259-66.
17. Trivedi N, Chauhan N, Vaidya V. Effectiveness and safety of dydrogesterone in regularization of menstrual cycle: a post-marketing study. Gynecol Endocrinol. 2016; 32(8): 667-71.
18. Guimarães I, Póvoa AM. Primary Dysmenorrhea: Assessment and Treatment. Rev Bras Ginecol Obstet. 2020; 42(8): 501-7.
19. Stute P. Dydrogesterone indications beyond menopausal hormone therapy: an evidence review and woman’s journey. Gynecol Endocrinol. 2021; 37(8): 683-8.
20. Taniguchi F, Ota I, Iba Y et al. The efficacy and safety of dydrogesterone for treatment of dysmenorrhea: An open-label multicenter clinical study. J Obstet Gynaecol Res. 2019; 45(1): 168-75.
21. Aydar CK, Coleman BD. Treatment of Primary Dysmenorrhea: A Double-Blind Study. JAMA. 1965; 192(11): 1003-5.
22. Gould CH. Dydrogesterone in teenage dysmenorrhoea. A multicentre trial in general practice. Practitioner. 1979; 222(1331): 718-23.
23. Tiranini L, Nappi RE. Recent advances in understanding/management of premenstrual dysphoric disorder/premenstrual syndrome. Fac Rev. 2022; 11: 11.
24. Khajehei M, Abdali K, Parsanezhad ME et al. Effect of treatment with dydrogesterone or calcium plus vitamin D on the severity of premenstrual syndrome. Int J Gynaecol Obstet. 2009; 105(2): 158-61.
25. Kerr GD, Day JB, Munday MR et al. Dydrogesterone in the treatment of the premenstrual syndrome. Practitioner. 1980; 224(1346): 852-5.
26. Panay N, Pritsch M, Alt J. Cyclical dydrogesterone in secondary amenorrhea: results of a double-blind, placebo-controlled, randomized study. Gynecol Endocrinol. 2007; 23(11): 611-8.
27. Hadaś K, Warenik-Szymankiewicz A, Halerz-Nowakowska B et al. [Repeated amenorrhea after body weight loss. Efficacy of treatment of estrogen and gestagen depending on the body mass index]. Ginekol Pol. 1999; 70(5): 383-8.
28. Battino S, Ben-Ami M, Geslevich Y et al. Factors associated with withdrawal bleeding after administration of oral dydrogesterone or medroxyprogesterone acetate in women with secondary amenorrhea. Gynecol Obstet Invest. 1996; 42(2): 113-6.
29. Katalinic A, Shulman LP, Strauss JF et al. A critical appraisal of safety data on dydrogesterone for the support of early pregnancy: a scoping review and meta-analysis. Reprod Biomed Online. 2022; 45(2): 365-73.
30. Walch K, Hefler L, Nagele F. Oral dydrogesterone treatment during the first trimester of pregnancy: the prevention of miscarriage study (PROMIS). A double-blind, prospectively randomized, placebo-controlled, parallel group trial. J Matern Fetal Neonatal Med. 2005; 18(4): 265-9.
31. Carp H. A systematic review of dydrogesterone for the treatment of recurrent miscarriage. Gynecol Endocrinol. 2015; 31(6): 422-30.
32. The ESHRE Guideline Group on RPL; Bender Atik R, Christiansen OB, Elson J et al. (2023) ESHRE guideline: recurrent pregnancy loss: an update in 2022. Hum Reprod Open. 2023(1): hoad002.
33. Wahabi HA, Fayed AA, Esmaeil SA et al. Progestogen for treating threatened miscarriage. Cochrane Database Syst Rev. 2018(8): CD005943.
34. Czajkowski K, Sienko J, Mogilinski M et al. Uteroplacental circulation in early pregnancy complicated by threatened abortion supplemented with vaginal micronized progesterone or oral dydrogesterone. Fertil Steril. 2007; 87(3): 613-8.
35. Das R, Rout RR, Tiwari RVC et al. Evaluation of per Vaginal Bleeding With Different Drugs in Successful Pregnancy in Patients With Recurrent Pregnancy Loss: An Original Research. J Pharm Bioallied Sci. 2022; 14(suppl 1): S193-5.
36. Ghosh S, Chattopadhyay R, Goswami S et al. Assessment of sub-endometrial blood flow parameters following dydrogesterone and micronized vaginal progesterone administration in women with idiopathic recurrent miscarriage: a pilot study. J Obstet Gynaecol Res. 2014; 40(7): 1871-6.
37. Kale AR, Kale AA, Yelikar K. A Comparative, Randomized Control Trial in Patients of Per Vaginal Bleeding Comparing Efficacy of Oral Dydrogesterone Versus Vaginal Progesterone in Successful Pregnancy Outcome for Patients with Recurrent Pregnancy Loss. J Obstet Gynecol India. 2021; 71(6): 591-5.
38. Kalinka J, Szekeres-Bartho J. The impact of dydrogesterone supplementation on hormonal profile and progesterone-induced blocking factor concentrations in women with threatened abortion. Am J Reprod Immunol. 2005; 53(4): 166-71.
39. Ott J, Egarter C, Aguilera A. Dydrogesterone after 60 years: a glance at the safety profile. Gynecol Endocrinol. 2022; 38(4): 279-87.
40. van der Linden M, Buckingham K, Farquhar C et al. Luteal phase support for assisted reproduction cycles. Cochrane Database Syst Rev. 2015; (7): CD009154.
41. Balasch J, Vanrell JA, Márquez M et al. Dehydrogesterone versus vaginal progesterone in the treatment of the endometrial luteal phase deficiency. Fertil Steril. 1982; 37(6): 751-4.
42. Fatemi HM, Popovic-Todorovic B, Papanikolaou E et al. An update of luteal phase support in stimulated IVF cycles. Hum Reprod Update. 2007; 13(6): 581-90.
43. Orazov MR, Radzinskiy VE, Nosenko EN et al. Combination therapeutic options in the treatment of the luteal phase deficiency. Gynecol Endocrinol. 2017; 33(suppl 1): 1-4.
44. Koninckx PR, Fernandes R, Ussia A et al. Pathogenesis Based Diagnosis and Treatment of Endometriosis. Front Endocrinol (Lausanne). 2021; 12: 745548.
45. Peng C, Huang Y, Zhou Y. Dydrogesterone in the treatment of endometriosis: evidence mapping and meta-analysis. Arch Gynecol Obstet. 2021; 304(1): 231-52.
46. Sun S, Zhang H, Zhong P et al. The Effect of Letrozole Combined with Dydrogesterone for Endometriosis in China: A Meta-Analysis. Biomed Res Int. 2021; 2021: 9946060.
47. Sukhikh GT, Adamyan LV, Dubrovina SOet al. Prolonged cyclical and continuous regimens of dydrogesterone are effective for reducing chronic pelvic pain in women with endometriosis: results of the ORCHIDEA study. Fertil Steril. 2021; 116(6): 1568-77.
48. de Carvalho BR. Dydrogesterone as an Option in the Medical Treatment of Endometriosis: A Brief Comment. Rev Bras Ginecol Obstet. 2022; 44(8): 802-3.
49. Stevenson JC, Durand G, Kahler E et al. Oral ultra-low dose continuous combined hormone replacement therapy with 0.5 mg 17β-oestradiol and 2.5 mg dydrogesterone for the treatment of vasomotor symptoms: results from a double-blind, controlled study. Maturitas. 2010; 67(3): 227-32.
50. Ren M, Ruan X, Gu L et al. Ultra-low-dose estradiol and dydrogesterone: a phase III study for vasomotor symptoms in China. Climacteric. 2022; 25(3): 286-92.
51. Nieto JJ, Cogswell D, Jesinger D et al. Lipid effects of hormone replacement therapy with sequential transdermal 17-beta-estradiol and oral dydrogesterone. Obstet Gynecol. 2000; 95(1): 111-4.
52. Kuba VM, Teixeira MA, Meirelles RMR et al. Dydrogesterone does not reverse the cardiovascular benefits of percutaneous estradiol. Climacteric. 2013; 16(1): 54-61.
53. Piróg M, Jach R, Kacalska-Janssen O. Differential effect of the ultra-low dose and standard estrogen plus dydrogesterone therapy on thrombin generation and fibrinolysis in postmenopausal women. Acta Obstet Gynecol Scand. 2017; 96(12): 1438-45.
54. Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases. BMJ. 2020; 371: m3873.
55. Fournier A, Mesrine S, Dossus L et al. Risk of breast cancer after stopping menopausal hormone therapy in the E3N cohort. Breast Cancer Res Treat. 2014; 145(2): 535-43.
56. Fournier A, Dossus L, Mesrine S et al. Risks of endometrial cancer associated with different hormone replacement therapies in the E3N cohort, 1992-2008. Am J Epidemiol. 2014; 180(5): 508-17.