Безопасностьометрия при непрерывной заместительной гормональной терапии 17b-эстрадиоло-эндопротезной заместительной гормональной терапии 17b-эстрадиолиин иниситисинисисиной

Abstract

The aim of the study was to determine the endometrial safety of oral 17/3- oestradiol combined continuously with dydrogesterone in preventing endometrial proliferation. The low dose group comprised three 52-week (13 cycles of 28 days) studies (two of which were double blind) using a 17ft- о estradiol dose of 1 mg daily combined with dydrogesterone 2,5; 5; 10 or 20 mg daily. The high dose group comprised two 24-week double-blind studies using a 17ft-oestradiol dose of 2 mg daily combined with dydrogesterone 2,5; 5; 10 or 15 mg daily. Endometrial safety was verified by aspiration endometrial biopsies. Inadequate progestational response was defined as proliferative endometrium, endometrial polyp, hyperplasia and carcinoma. Endometrial protection was achieved with dydrogesterone at doses of 5 mg or higher combined with 1 or 2 mg 17^-oestradiol. So, 5 mg daily dydrogesterone appears to be the lowest effective dose to ensure endometrial safety in a continuous combined regimen with 1 or 2 mg 17p-oestradiol.

Keywords

степень защиты эндометрия / 17b-эстрадиол / дидрогестерон

References

[1] Brinton L. A., Hoover R. N. Estrogen replacement therapy and endometrial cancer risk: unresolved issues // Obstet. Gynecol. — 1993. — Vol. 81.-P. 265-271.

[2] Shapiro S., Kelly J. P, Rosenberg L., et al. Risk of localised and widespread endometrial cancer in relation to recent and discontinued use of conjugated estrogens //New Engl. J. Med. - 1985. - Vol. 313. - P. 969-972.

[3] Grady D., GebretsadikT., Kerlikowske K., et al. Hormone replacement therapy and endometrial cancer risk: a meta-analysis // Obstet. Gynecol. — 1995. — Vol. 85. - P. 304-313.

[4] WhiteheadM. I., FraserD. The effects of estrogens and progestogens on the endometrium // Obstet. Gynecol. Clin. North. Am. — 1987. - Vol. 14. - P. 299-320.

[5] Varma T. R. Effect of long-term therapy with estrogen and progesterone on the endometrium of post-menopausal women // Acta Obstet. Gynecol. Scand. — 1985. — Vol. 64. - P. 41-46.

[6] Voigt L. R, Weiss N. S., Chur J., et al. Progestogen supplementation of exogenous oestrogens and risk of endometrial cancer//Lancet. — 1991. — Vol. 338. - P. 274-277.

[7] Vermorken A. J. M., Sultan С. H., Goos С. M. A. A. Dydrogesterone has no peripheral (anti)-androgenic properties // In Vivo. — 1987. — Vol. 1. - P. 167-172.

[8] Ottosson U. B., Johansson B. G., vonSchoultz B. Subtractions of high- density lipoprotein cholesterol during estrogen replacement therapy: a comparison between progestogens and natural progesterone //Am. J. Obstet. Gynecol. — 1985. — Vol. 115. - P. 746-750.

[9] Lacey R. W., Howson G. L., Sampson G. A. Safety of progestins: effects of dydrogesterone on blood lipids//Вr. J. Clin. Pract. — 1983. — Suppl. 24. -P. 4-10.

[10] Martin A. I. Progestins: a review of safety and tolerance in long-term administration // Modern Med. — 1986. - Vol. 31.-P. 1-7.

[11] Gambrell R. D., Bagnell C. A., Greenblatt R. B. Role of estrogens and progesterone in the etiology and prevention of endometrial cancer // Am. J. Obstet. Gynecol. — 1983. — Vol. 146. - P. 696-707.

[12] Lane G., Siddle N. C., Ryder T. A., etal. Effect of dydrogesterone on the 81

[13] oestrogenized postmenopausal endometrium // Br. J. Obstet.

[14] Gynaecol. — 1986. — Vol. 93. — P. 55-62.

[15] Lane G., Siddle N. C, Ryder T. A., et al. Endometrial responses, sideeffects and bleeding patterns in postmenopausal women using various doses of dydrogesterone in combination with conjugated oestrogens // Br. J. Clin. Pract. — 1983. - Vol. 24. - P. 23-26.

[16] Burch D. J., SpowartK. J. M., JessingerD. K, etal. A dose-ranging study of the use of cyclical dydrogesterone with continuous 17ft- oestradiol // Br. J. Obstet. Gynaecol. - 1995. - Vol. 102. - P. 243-248.

[17] Committee for Proprietary Medicinal Products (CPMP). Points to consider on Hormone Replacement Therapy. — London, 19 November 1997.

[18] Voetberg G. A., NetelenbosJ. C, Kenemans P, etal. Estrogen replacement therapy continuously combined with four different dosages of dydrogesterone: effect on calcium and lipid metabolism //J. Clin.Endocrinol. Metab. — 1994. — Vol. 79. - P. 1465-1469.

[19] Mijatovic V., Kenemans P, NetelenbosJ. C., etal. Oral 17ft- estradiol continuously combined with dydrogesterone lowers serum lipoprotein(a) concentrations in healthy postmenopausal women //J. Clin. Endocrinol. Metab. — 1997. — Vol. 82. - P. 3543-3547.

[20] Kurman R. J., Mazur M. T. Benign diseases of the endometrium // Kurman R. J. (ed.) Blaustein’s pathology of the female genital tract. — Berlin: Springer, 1994. — P. 367- 409.

[21] Wolfe S. A., Mackles A. Malignant lesions arising from benign endometrial polyps // Obstet.Gynecol. — 1962. — Vol. 20. — P. 542-550.

[22] Mittal K, Schwartz L., Goswami S., Demopoulos R. Estrogen and progesterone receptor expression in endometrial polyps // Int. J. Gynecol. Pathol. — 1996. — Vol. 15. - P. 345-348.

[23] Woodruff J. D., PickarJ. H. Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone // Am. J. Obstet. Gynecol. — 1994. — Vol. 170. - P. 1213-1223.

[24] The Writing Group for the PEP! trial. Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The postmenopausal estrogen/ progestin intervention trial// JAMA. — 1996. — Vol. 275. - P. 370-375.

[25] Van der Mooren M. J., HanselaarA. G., Born G. F., Rolland R. Changes in the withdrawal bleeding pattern and endometrial histology during 17/3-oestradiol- dydrogesterone therapy in postmenopausal women: a 2-year prospective study//Maturitas. — 1994. - Vol. 20. - P. 175-80.

[26] Ferenczy A., Gelfand M. M. Endometrial histology and bleeding patterns in post-menopausal women taking sequential, combined estradiol and dydrogesterone // Maturitas. — 1997. - Vol. 26. - P. 219-226.

[27] Cushing K. L, Weiss N. S., Voigt L. F, etal. Risk of endometrial cancer in relation to use of low-dose, unopposed estrogens // Obstet. Gynecol. - 1998. - Vol. 91. - P. 35-39.

[28] Comerci J. T., Fields A. L., Runowicz C. D., Goldberg G. L. Continuous low-dose combined hormone replacement therapy and the risk of endometrial cancer// Gynecol. Oncol. — 1997. — Vol. 64. — P. 425-430.

[29] Weiderpass E., Adami H. O., Baron J. A., et al. Risk of endometrial cancer following estrogen replacement with and without progestins // J. Natl. Cancer Inst. — 1999. - Vol. 91.-P. 1131-1137

RIGHTS & PERMISSIONS

Eсо-Vector