GynecologyGynecology2079-56962079-5831Consilium Medicum10662910.26442/20795696.2022.6.201685Research ArticleEffect of combined oral contraceptives with estrogen identical to natural estrogen on the metabolic profile and body composition in females during the menopausal transitionKomedinaVeronika I.<p>Graduate Student, Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology</p>komedina.veronika@gmail.comhttps://orcid.org/0000-0002-9084-5044YurenevaSvetlana V.<p>D. Sci. (Med.), Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology</p>syureneva@gmail.comhttps://orcid.org/0000-0003-2864-066XKuznetsovSergey Yu.<p>Cand. Sci. (Med.), Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology</p>s_kuznetsov@oparina4.ruKulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology211220222464874932204202215062022Copyright © 2022, Consilium Medicum2022<p><strong>Aim. </strong>To study the effect of combined oral contraceptives (COC) with estrogen identical to natural estrogen on the metabolic profile and body composition in females during the menopausal transition.</p>
<p><strong>Materials and methods. </strong>Females in the menopausal transition who needed contraception were divided into two groups. Group 1 (19 patients) received COCs containing estradiol valerate/dienogest (E2V/DNG) with a dynamic dosing regimen; Group 2 (19 patients) received monophasic COCs containing 17-estradiol/nomegestrol acetate (E2/NOMAC) for 6 months. Blood pressure (BP), parameters of carbohydrate and lipid metabolism, leptin, adiponectin, C-reactive protein, uric acid, and body composition by dual-energy X-ray absorptiometry were assessed initially and after the 6 months of therapy.</p>
<p><strong>Results. </strong>No significant changes in weight and body composition after 6 months of COC use were found in both groups. COCs with E2V/DNG had no significant effect on BP and all assessed metabolic parameters. Females taking COCs with E2/NOMAC showed increased fasting glucose of 4.85 (0.43) and 5.30 (0.37) mmol/L (<em>p</em>=0.002), insulin of 4.97 (2.35) and 8.82 (4.67) U/mL (<em>p</em>=0.012), NOMA index of 1.06 (0.54) and 1.88 (0.75); <em>p</em>=0.010 compared to baseline. However, the parameters remained within the reference values.</p>
<p><strong>Conclusion. </strong>COCs containing estrogens identical to natural estrogens do not affect body composition and have no significant adverse effect on BP and metabolic parameters in females during the menopausal transition, indicating that the use of these agents is acceptable from the perspective of their metabolic effects in this group of patients.</p>menopausal transitioncombined oral contraceptivesestradiol valeratenomegestrol acetatedienogestbody compositionlipidscarbohydrate metabolismменопаузальный переходкомбинированные оральные контрацептивыэстрадиола валератномегэстрола ацетатдиеногесткомпозиционный состав телалипидыуглеводный обмен[Прилепская В.Н., Серов В.Н., Назарова Н.М., и др. Руководство по контрацепции. Под ред. проф. В.Н. Прилепской. 5-е изд., доп. М.: МЕДпресс-Информ, 2018 [Prilepskaya VN, Serov VN, Nazarova NM, et al. Rukovodstvo po kontracepsii. Pod red. prof. VN Prilepskaia. 5-e izd., dop. Moscow: MEDpress-Inform, 2018 (in Russian)].][Cho MK. Use of Combined Oral Contraceptives in Perimenopausal Women. Chonnam Med J. 2018;54(3):153. DOI:10.4068/cmj.2018.54.3.153][Юренева С.В., Комедина В.И., Кузнецов С.Ю. Прибавка массы тела у женщин в перименопаузе: методы оценки композиционного состава тела и тактика ведения. Акушерство и гинекология. 2020;2:56-61 [Yureneva SV, Komedina VI, Kuznetsov SYu. Weight gain in perimenopausal women: methods for assessing the body composition and maintenance tactics. Akusherstvo i Ginekologiya. 2020;2:56-61 (in Russian)]. DOI:10.18565/aig.2020.2.56-61][Gallo MF, Lopez LM, Grimes DA, et al. Combination contraceptives: effects on weight. Cochrane Database Syst Rev. 201429;(1):CD003987. DOI:10.1002/14651858.CD003987.pub5][Grandi G, Napolitano A, Cagnacci A. Metabolic impact of combined hormonal contraceptives containing estradiol. Expert Opin Drug Metab Toxicol. 2016;12(7):779-87. DOI:10.1080/17425255.2016.1190832][Sitruk-Ware R, Nath A. Characteristics and metabolic effects of estrogen and progestins contained in oral contraceptive pills. Best Pract Res Clin Endocrinol Metab. 2013;27(1):13-24. DOI:10.1016/j.beem.2012.09.004][Bastianelli C, Farris M, Rosato E, et al. Pharmacodynamics of combined estrogen-progestin oral contraceptives: Effects on metabolism. Expert Rev Clin Pharmacol. 2016:17512433.2017.1271708. DOI:10.1080/17512433.2017.1271708][El Khoudary SR, Aggarwal B, Beckie TM, et al. Menopause Transition and Cardiovascular Disease Risk: Implications for Timing of Early Prevention: A Scientific Statement from the American Heart Association. Circulation. 2020;142(25):506-32. DOI:10.1161/CIR.0000000000000912][Messina C, Albano D, Gitto S, et al. Body composition with dual energy X-ray absorptiometry: From basics to new tools. Quant Imaging Med Surg. 2020;10:1687-98. DOI:10.21037/QIMS.2020.03.02][Драпкина О.М., Шепель Р.Н. Оценка уровня физической активности у пациентов с избыточной массой тела и ожирением в Российской Федерации (ФАКТОР-РФ): обоснование и дизайн исследования. Профилактическая медицина. 2020;23(3):7-19. [Drapkina OM, Shepel RN. Assessment of the level of physical activity in patients with overweight and obesity in the Russian Federation (FACTOR-RF): argumentation and study design. Profilakticheskaia meditsina. 2020;23(3):7-19 (in Russian)]. DOI:10.17116/profmed2020230317][Grandi G, Piacenti I, Volpe A, et al. Modification of body composition and metabolism during oral contraceptives containing non-androgenic progestins in association with estradiol or ethinyl estradiol. Gynecol Endocrinol. 2014;30(9):676-80. DOI:10.3109/09513590.2014.922947][Paoletti AM, Lello S, Di Carlo C, et al. Effect of Estradiol valerate plus dienogest on body composition of healthy women in the menopausal transition: a prospective one-year evaluation. Gynecol Endocrinol. 2016;32(1):61-4. DOI:10.3109/09513590.2015.1079175][Manuela N, Maria Elena M, Valentina C, et al. Body composition and psychological improvement in healthy premenopausal women assuming the oral contraceptive containing micronized estradiol (E2) and nomegestrol acetate (NOMAC). Gynecol Endocrinol. 2017;33(12):958-62. DOI:10.1080/09513590.2017.1322574][Napolitano A, Zanin R, Palma F, et al. Body composition and resting metabolic rate of perimenopausal women using continuous progestogen contraception. Eur J Contracept Reprod Heal Care. 2016;21(2):168-75. DOI:10.3109/13625187.2015.1079610][Cagnacci A, Arangino S, Baldassari F, et al. A comparison of the central effects of different progestins used in hormone replacement therapy. Maturitas. 2004;48(4):456-62. DOI:10.1016/j.maturitas.2003.10.003][Liu P, Ji Y, Yuen T, et al. Blocking FSH induces thermogenic adipose tissue and reduces body fat. Nature. 2017;546(7656):107-12. DOI:10.1038/nature22342][Junge W, Mellinger U, Parke S, Serrani M. Metabolic and Haemostatic Effects of Estradiol Valerate/Dienogest, a Novel Oral Contraceptive. Clin Drug Investig. 2011;31(8):573-84. DOI:10.2165/11590220-000000000-00000][Ågren UM, Anttila M, Mäenpää-Liukko K, et al. Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol compared with one containing levonorgestrel and ethinylestradiol on haemostasis, lipids and carbohydrate metabolism. Eur J Contracept Reprod Heal Care. 2011;16(6):444-57. DOI:10.3109/13625187.2011.604450][Lopez LM, Grimes DA, Schulz KF. Steroidal contraceptives: effect on carbohydrate metabolism in women without diabetes mellitus. In: LM Lopez, ed. Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd, 2012. DOI:10.1002/14651858.CD006133.pub4][Wagner JD, Thomas MJ, Williams JK, et al. Insulin sensitivity and cardiovascular risk factors in ovariectomized monkeys with estradiol alone or combined with nomegestrol acetate. J Clin Endocrinol Metab. 1998;83(3):896-901. DOI:10.1210/jcem.83.3.4628][Lee SR, Choi WY, Heo JH, et al. Progesterone increases blood glucose via hepatic progesterone receptor membrane component 1 under limited or impaired action of insulin. Sci Rep. 2020;10:16316. DOI:10.1038/s41598-020-73330-7]