ISSLEDOVANIE EFFEKTIVNOSTI MIKRODOZI-ROVANNOY ESTROGEN-GESTAGENNOY TERAPIIV PROFILAKTIKE POSTMENOPAUZAL'NOGO OSTEOPOROZA I KORREKTsII KLIMAKTERIChESKIKh NARUShENIY
https://doi.org/10.14341/osteo2009210-17
Abstract
Although the minimal dose of 17β-estradiol in hormone replacement regimens was originally considered to be 2 mg/day, it is now increasingly accepted that a lower dose of 1 mg/day is effective in protecting women from the detrimental effects of the menopause and has a better safety profile. The aim of this study was to investigate effectiveness and tolerability of minimal dose of hormone replacement therapy (HRT) - femoston 1/5 in postmenopausal women with spine osteopenia.
Study comprised 26 postmenopausal women aged 45-65 years with T-score L2-L4 <1.0 and >2.5 SD. Treated group consisted of 16 women (average age 54.8+5.59 years and postmenopausal age 6.81+4.59 years) received femoston 1/5 (17β-estradiol 1 mg/ daily continuously combined with dydrogesterone 5 mg/daily) for 12 months. Control group included 10 subjects (average age 56.7+4.11 years and postmenopausal age 11.5+8.09 years). BMD and biochemical parameters were measured at baseline and in 6 and 12 months and climacteric symptoms were assessed at baseline and in 1, 3, 6 and 12 months.
The increase in BMD were seen in lumbar spine +5.2%, total proximal femur +2.1% and trochanter +3.1% (р<0.01 vs. baseline in 12 months) in treated group. BMD significantly decreased in total proximal femur -1.3% and Ward's triangle -2% (p<0.05 vs. baseline in 12 months) and in femoral neck -0.6% (p<0.01 vs. baseline in 6 months) in control group. There was a lowering in PTH from 72.7+23.2 to 58.2+12.8 (p<0.05), alkaline phosphatase from 78.2+21.1 to 69.8+19.1 U/l (p<0.05 vs baseline, p<0.01 vs control) and osteocalcin from 33.0+10.1 to 25.4+9.28 ng/ml (p<0.05) in treated group in 6 months. We also found an increase in PTH from 46.9+13.4 to 54.9+11.1 pg/ml (p<0.05) and alkaline phosphatase from 86.0+15.6 to 100.0+15.0 U/l (p<0.05) in 6 months in controls. Treatment with femoston 1/5 improved blood lipid panel and acute climacteric symptoms. Modified menopausal index significantly diminished in the first month of the therapy (p<0.001). Tolerability of HRT was satisfactory.
Conclusions: The lower dose of oestrogen effectively increases BMD, lowering bone turnover, and improves calcium homeostasis, blood lipid profile and acute climacteric symptoms in postmenopausal women with osteopenia.
Study comprised 26 postmenopausal women aged 45-65 years with T-score L2-L4 <1.0 and >2.5 SD. Treated group consisted of 16 women (average age 54.8+5.59 years and postmenopausal age 6.81+4.59 years) received femoston 1/5 (17β-estradiol 1 mg/ daily continuously combined with dydrogesterone 5 mg/daily) for 12 months. Control group included 10 subjects (average age 56.7+4.11 years and postmenopausal age 11.5+8.09 years). BMD and biochemical parameters were measured at baseline and in 6 and 12 months and climacteric symptoms were assessed at baseline and in 1, 3, 6 and 12 months.
The increase in BMD were seen in lumbar spine +5.2%, total proximal femur +2.1% and trochanter +3.1% (р<0.01 vs. baseline in 12 months) in treated group. BMD significantly decreased in total proximal femur -1.3% and Ward's triangle -2% (p<0.05 vs. baseline in 12 months) and in femoral neck -0.6% (p<0.01 vs. baseline in 6 months) in control group. There was a lowering in PTH from 72.7+23.2 to 58.2+12.8 (p<0.05), alkaline phosphatase from 78.2+21.1 to 69.8+19.1 U/l (p<0.05 vs baseline, p<0.01 vs control) and osteocalcin from 33.0+10.1 to 25.4+9.28 ng/ml (p<0.05) in treated group in 6 months. We also found an increase in PTH from 46.9+13.4 to 54.9+11.1 pg/ml (p<0.05) and alkaline phosphatase from 86.0+15.6 to 100.0+15.0 U/l (p<0.05) in 6 months in controls. Treatment with femoston 1/5 improved blood lipid panel and acute climacteric symptoms. Modified menopausal index significantly diminished in the first month of the therapy (p<0.001). Tolerability of HRT was satisfactory.
Conclusions: The lower dose of oestrogen effectively increases BMD, lowering bone turnover, and improves calcium homeostasis, blood lipid profile and acute climacteric symptoms in postmenopausal women with osteopenia.
About the Authors
L A MarchenkovaA V Dreval'
I V Kryukova
M V Vishnyakova
R S Tishenina
N V Balashova
M P Rubin
References
1. Балан В.Е., Вихляева Е.М., Зайдиева Я.З. и соавт. Менопаузаль-ный синдром (клиника, диагностика, профилактика и заместительная гормональная терапия) // М.-1996. 64 с.
2. А.В. Древаль, Л.А. Марченкова, Е.Ю. Полякова, И.В. Крюкова, Р.С. Тишенина, Н.Д. Гаспарян, Д.В. Григорьева, А.В. Королева. Эффективность фемостона в лечении менопаузального синдрома у женщин, получающих кортикостероидную терапию // Остеопороз и остеопатии, 2003. № 2. С. 14-18.
3. А.В. Древаль, Л.А. Марченкова, Е.Ю. Полякова, И.В. Крюкова, РС. Тишенина, Н.Д. Гаспарян, Д.В. Григорьева, А.В. Королева. Опыт лечения препаратом фемостон женщин в перименопаузе, получающих перо-ральную кортикостероидную терапию // Акушерство и женские болезни, Спб-2004. №2, С. 55-59.
4. А.В.Древаль, Л.А.Марченкова, Р.С.Тишенина, Б.И.Минченко, Г.А.Оноприенко, В.И.Шумский, И.А.Комиссарова, Я.Р.Нарциссов. Комбинация заместительной гормональной терапии с препаратами естественных метаболитов (глицином и лимонтаром) в лечении менопау-зального синдрома // Проблемы эндокринологии, 1999. №4. С.19-24.
5. Медицина климактерия. Под редакцией Сметник В.П. // Ярославль. «Издательство Литера». 2006. 847 с.
6. Шестакова И.Г., Сметник В.П. Влияние ЗГТ препаратом Фемостон 2/10 на массу тела и углеводный обмен у женщин в перименопаузе. // Проблемы репродукции. 2001. т. 7. №2
7. Amy J.J. Femoston: effects on bone and quality-of-life // Eur Menop J. 1995. V.2. P. 16-22.
8. Anderson G.L., Limacher M., Assaf A.R. et al. Women's Health Initiative Steering Committee. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: Women's Health Initiative randomized controlled trial // JAMA. 2004. V.14. P. 1704-1712.
9. Arrenbrecht S., Caubel P., Garnero P. et al. The effect of continuous oestradiol with intermittent norgestimate on bone mineral density and bone turnover in post-menopausal women // Maturitas. 2004. V. 48. P. 197-207.
10. Cauley J.A., Robbins J., Chen Z. et al. Effect of estrogen plus progestin on risk of fracture and bone mineral density. WHY randomized trial // JAMA. 2003. V.290/ P. 1729-1738.
11. Dambacher M.D., Schacht E., Scharia S. Alfacalcidol // ed. Veenman Drukkers. 1998., 67.p.
12. Delmas P.D., Confavreux E., Garnero P. et al. A combination of low doses of 17pE2 and NETA prevents bone lose and normalizes bone tuenover in postmenopausal women // Osteoporosis Int. 2000. V. 11. P.177-187.
13. De Valk-De Roo G.W., Netelenbos J.C., Peters-Muller IRA et. al. Continuously combined hormone replacement therapy and bone turnover: the influence of dydrogesterone dose, smoking and initial degree of bone turnover // Maturitas. 1997. V. 28. P. 153-162.
14. Gelfand M.M., Fugere P., Bissonnette F. et. al. Conjugated estrogens combined with sequential dydrogesterone or medroxyprogesterone actetate in posmenopausal women: effects on lipoproteins, glucose tolerance, endometrial histology, and bleeding // Menop. 1997. V. 4. P. 10-18.
15. Gelfand M., Fugere P., Bissonnette F. Cardiovascular risk factors during sequentially combined 17p-oestradiol and dydrogesterone (femoston); results from a one-year study in posmenopausal women // Maturitas. 1997. V. 26. P. 125-132.
16. Grady D., Brown J.S., Vittinghoff E. et al. HERS Research Group. Postmenopausal hormones and incontinence: the Heart and Estrogen/ Progestin ReplacementStudy // Obstet. Gynecol. 2001. V. 97. P. 116-120.
17. Hanggi W., Lippuner K., Rieser W. et al. Long term influence of different postmenopausal hormone replacement regimes on serum lipids and lipoprotein(a): a randomized study // Br J Obst Gynaecol. 1997. V. 104. P. 708-717.
18. Kenemans P. Menopause, hormone replacement therapy and menopausal symptoms // J Epidemiol Biostat. 1999. V.4. P. 141-146.
19. Lees B., Stevenson J.C. The Prevention of Osteoporosis Using Sequential Low-Dose Hormone Replacement Therapy with Estradiol-17p and Dydrogesterone // Osteoporosis International. 2001. V. 12. P. 251-258.
20. Nilsson K., Heimer G. Low-dose 17ft-oestradiol during maintenance therapy - a pharmacokinetic and pharmacodynamic study // Maturitas. 1995. V. 21. P. 230-245.
21. Nordin B.E.C. et al. Calcium, phosphate and magnesium metabolism. Edinburgh, 1976. P.469-500.
22. Paschalis E.P., Boskey A.L., Kassem M., Eriksen E.F. Effect of hormone replacement therapy on bone quality in early postmenopausal women // J. Bone Miner. Res. 2003. V. 18. P. 955-959.
23. Pornel B., Chevallier O., Netelenbos J.C. Oral 17p-estradiol (1 mg) continuously combined with dydrogesterone improves the serum lipid profile of posmenopausal women // Menopause. 2002.V. 9, N, 3, P. 171-178.
24. Prelevic G.M., Bartram C., Wood J., et al. Comparative effects on bone mineral density of tibolone, transdermal estrogen and oral estrogen progestagen therapy in postmenopausal women. // Gynecol. Endocrinol. 1996. V. 6. P. 413-420.
25. Ralston S.H. Analysis of gene expression in human bone biopsy by polymerase chain reaction: evidence for enhanced cytokine expression in postmenopausal osteoporosis. // J. Bone Mineral Research. 1994. V.9. P. 883-890.
26. Rejnmark L., Vestergaard P., Toffeng C.L. et al. Response rates to oestrogen treatment in perimenopausal women: 5-year data from The Danish Osreoporosis Prevention Study (DOPS) // Maturitas. 2004. V. 48. P. 307-320.
27. Stevenson J.C., Teter P., Lees B. 17p-Estradiol (1mg/day) continuously combined with dydrogesterone (5, 10 or 20 mg/day) increases bone mineral density in postmenopausal women // Maturitas. 2001. V. 38. P. 197-203.
28. Wells G., Tugwell P., Shea B. et al. Meta-analysis of the efficacy of hormon replacement therapy in treating and preventing osteoporosis in postmenopausal women. // Endocr. Rew. 2002. V.23. P.529-539.
Review
For citations:
Marchenkova L.A., Dreval' A.V., Kryukova I.V., Vishnyakova M.V., Tishenina R.S., Balashova N.V., Rubin M.P. ISSLEDOVANIE EFFEKTIVNOSTI MIKRODOZI-ROVANNOY ESTROGEN-GESTAGENNOY TERAPIIV PROFILAKTIKE POSTMENOPAUZAL'NOGO OSTEOPOROZA I KORREKTsII KLIMAKTERIChESKIKh NARUShENIY. Osteoporosis and Bone Diseases. 2009;12(2):10-17. (In Russ.) https://doi.org/10.14341/osteo2009210-17
Views:
450
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0).
Email this article 
