Characteristics of menstrual function and blood test parameters in women with uterine fibroids using multiphasic and monophasic combined hormonal contraceptives

Abstract

BACKGROUND: In some cases, women with uterine fibroids have heavy menstrual bleeding and dysmenorrhea. Combined hormonal contraceptives are used both for contraception and to alleviate the clinical manifestations of uterine fibroids that do not require surgical treatment. Publications on the effect of combined hormonal contraceptives on the clinical course of uterine fibroids are rare.

AIM: The aim of this study was to evaluate the characteristics of menstrual function, as well as clinical and biochemical blood test parameters, blood lipid spectrum and hemostatic screening test parameters in dynamics in women with uterine fibroids using low-dose multiphasic and monophasic combined hormonal contraceptives with ethinyl estradiol.

MATERIALS AND METHODS: This study included 148 women, out of whom there were 118 patients with uterine fibroids without indications for surgical treatment [54 patients used multiphasic (ethinyl estradiol ans desogestrel) and monophasic (ethinyl estradiol and various gestagens) combined hormonal contraceptives, 64 patients did not] and 30 healthy participants using combined hormonal contraceptives with ethinyl estradiol. At baseline, after six and 12 months, the study participants were assessed for the duration, volume, and painfulness or painlessness (visual analogue scale, McGill pain questionnaire) of menstrual blood loss, as well as laboratory examination parameters.

RESULTS: In women with uterine fibroids using various combined hormonal contraceptives (n = 54), a decrease in the duration (5.6 ± 1.2, 4.1 ± 1.0, and 4.1 ± 1.2 of a day respectively; p < 0.05) and volume of menstrual bleeding was noted after 6 and 12 months. 6 of 16 patients with uterine fibroids and heavy menstrual bleeding used combined hormonal contraceptives (2 patients used multiphasic contraceptives, and 4 others monophasic ones). In these 6 women, normal hemoglobin (124–132 g/l) and ferritin (35.4–42.4 μg/l) levels were recorded after 12 months. In patients with uterine fibroids, a reduction in dysmenorrhea or a decrease in its intensity was observed with the use of multiphasic (n = 7; 5.1 ± 1.5, 2.0 ± 0.7, and 1.6 ± 0.5 of a point, respectively) and monophasic (n = 2; 4.6 ± 1.2, 3.7 ± 1.1, and 3.0 ± 0.4 of a point, respectively) combined hormonal contraceptives (p < 0.05). No changes were recorded in the initially normal parameters of biochemical blood analysis, lipidogram and coagulogram in the study participants.

CONCLUSIONS: The use of multi- and monophasic combined hormonal contraceptives with ethinyl estradiol in patients with uterine fibroids leads to a decrease in the duration and volume of menstrual blood loss. It helps maintain normal levels of hemoglobin and ferritin and reduce the frequency and intensity of dysmenorrhea associated with uterine fibroids. Apart from that, it does not lead to changes in the parameters of biochemical blood analysis, blood lipid spectrum and hemostatic screening in the absence of contraindications to the use these drugs.

Keywords

uterine fibroids / combined hormonal contraceptives / dysmenorrhea / heavy menstrual bleeding

References

[1] Arutyunova EE, Katkova AS, Rapoport SI. Ethnogeography of uterine fibroids: epidemiology, age and racial differences, types of surgical interventions. Consilium Medicum. 2018;20(6):26–30. EDN: UZEXJI doi: 10.26442/2075-1753_2018.6.26-30

[2] Арутюнова Е.Э., Каткова А.С., Буралкина Н.А. Этногеография миомы матки: эпидемиология, возрастные и расовые различия, виды оперативных вмешательств // Consilium Medicum. 2018. Т. 20, № 6. С. 26–30. EDN: UZEXJI doi: 10.26442/2075-1753_2018.6.26-30

[3] National Collaborating Centre for Women’s and Children’s Health (UK). Heavy Menstrual Bleeding Clinical. London: RCOG Press; 2007.

[4] National Collaborating Centre for Women’s and Children’s Health (UK). Heavy Menstrual Bleeding Clinical. London: RCOG Press, 2007.

[5] Dolgushina NV, Adamyan LV, Sheshko EL. Late reproductive age of a woman: risks of reproductive dysfunction (literature review). Russian Journal of Human Reproduction. 2023;29(4):99–106. EDN: MLFZAQ doi: 10.17116/repro20232904199

[6] Долгушина Н.В., Адамян Л.В., Шешко Е.Л. Поздний репродуктивный возраст женщины: риски нарушения репродуктивной функции (обзор литературы) // Проблемы репродукции. 2023. Т. 29, № 4. С. 99–106. EDN: MLFZAQ doi: 10.17116/repro20232904199

[7] Medical eligibility criteria for contraceptive use. 5th ed. Geneva: World Health Organization; 2015. (In Russ.) [cited 2024 Sep 12] Available from: https://www.who.int/ru/publications/i/item/9789241549158

[8] Медицинские критерии приемлемости для использования методов контрацепции. 5-е изд. Всемирная организация здравоохранения. Европейское регионарное бюро, 2015. Режим доступа: https://www.who.int/ru/publications/i/item/9789241549158. Дата обращения: 12.09.2024.

[9] Federal State Budgetary Institution National Medical Research Center of Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov of the Ministry of Health of the Russian Federation, Russian Society of Obstetricians and Gynecologists, Russian Society of Contraception. National Medical Eligibility Criteria for Contraceptive Methods. Adapted from the document “WHO Medical Eligibility Criteria for the Use of Contraceptive Methods, 5th Edition, 2015”. Moscow; 2023. [cited 2024 Sep 12] Available from: https://phlebounion.ru/files/uploads/News/files/2023%20Национальные%20критерии%20приемлемости%20контрацепции%202023.pdf?ysclid=m5uvzra16w271625183. (In Russ.)

[10] ФГБУ НМИЦ акушерства, гинекологии и перинатологии им. академика В.И. Кулакова Министерства Здравоохранения РФ Российское общество акушеров-гинекологов Российское общество по контрацепции. Национальные медицинские критерии приемлемости методов контрацепции. Адаптированный документ «Медицинские критерии приемлемости использования методов контрацепции ВОЗ, 5 издание, 2015». Москва, 2023. Режим доступа: https://phlebounion.ru/files/uploads/News/files/2023%20Национальные%20критерии%20приемлемости%20контрацепции%202023.pdf?ysclid=m5uvzra16w271625183. Дата обращения: 12.09.2024.

[11] Russian Society of Obstetricians and Gynecologists. Uterine fibroids. Clinical recommendations. Moscow: Ministry of Health of the Russian Federation; 2020. (In Russ.) [cited 2024 Sep 12] Available from: https://cr.minzdrav.gov.ru/schema/257_1

[12] Российское общество акушеров-гинекологов. Миома матки. Клинические рекомендации. Москва: Минздрав РФ, 2020. Режим доступа https://cr.minzdrav.gov.ru/schema/257_1. Дата обращения: 12.09.2024.

[13] Russian Society of Obstetricians and Gynecologists. Abnormal uterine bleeding. Clinical recommendations. Moscow: Ministry of Health of the Russian Federation, 2021. (In Russ.) [cited 2024 Sep 12] Available from: https://cr.minzdrav.gov.ru/schema/645_1

[14] Российское общество акушеров-гинекологов. Аномальные маточные кровотечения. Клинические рекомендации. Москва: Минздрав РФ, 2021. Режим доступа: https://cr.minzdrav.gov.ru/schema/645_1. Дата обращения: 12.09.2024.

[15] Munro MG, Critchley HOD, Fraser IS, FIGO Menstrual Disorders Committee. The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions. Int J Gynecol Obstet. 2018;143(3):393–408. doi: 10.1002/ijgo.12666

[16] Munro M.G., Critchley H.O.D., Fraser I.S., FIGO Menstrual Disorders Committee. The two FIGO systems for normal and abnormal uterine bleeding symptoms and classification of causes of abnormal uterine bleeding in the reproductive years: 2018 revisions // Int J Gynecol Obstet. 2018. Vol. 143, N 3. P. 393–408. doi: 10.1002/ijgo.12666

[17] Moxov EM, Kadyakov VA, Sergeev AN, et al. Pain scoring systems and their application features in medicine (literature review). Verkhnevolzhskij medical journal. 2019;18(2):34–37. EDN: DEYKPY

[18] Мохов Е.М., Кадыков В.А., Сергеев А.Н. и др. Оценочные шкалы боли и особенности их применения в медицине (обзор литературы) // Верхневолжский медицинский журнал. 2019. Т. 18, № 2. С. 34–37. EDN: DEYKPY

[19] Melzack R. The McGill Pain Questionnaire: major properties and scoring methods. Pain. 1975;1(3):277–299. doi: 10.1016/0304-3959(75)90044-5

[20] Melzack R. The McGill Pain Questionnaire: major properties and scoring methods // Pain. 1975. Vol. 1, N 3. Р. 277–299. doi: 10.1016/0304-3959(75)90044-5

[21] Gricenko YaV, Konstantinova OD, Cherkasov SV. Myoma of the uterus in the modern world: current issues pathogenesis, diagnosis and treatmen. Bulletin of the Orenburg Scientific Center of the Ural Branch of the Russian Academy of Sciences. 2012;(3). EDN: NTOMCT

[22] Гриценко Я.В., Константинова О.Д., Черкасов С.В. Миома матки в современном мире: актуальные вопросы патогенеза, диагностики и лечения // Бюллетень оренбургского научного центра УРо РАН. 2012. № 3. EDN: NTOMCT

[23] Tikhomirov AL. Myoma, pathogenetic rationale for organ-preserving treatment. Moscow; 2013. 319 p. (In Russ.)

[24] Тихомиров А.Л. Миома, патогенетическое обоснование органосохраняющего лечения. Москва; 2013. 319 с.

[25] Tranexamic acid. Instructions for use. In: Vidal [Internet]. (In Russ.) [cited 2024 Sep 12] Available from: https://www.vidal.ru/drugs/molecule/1070.

[26] Транексамовая кислота. Инструкция по применению. В: Видаль [Internet]. Режим доступа: https://www.vidal.ru/drugs/molecule/1070. Дата обращения: 12.09.2024.

[27] Prilepskaya VN, Mezhevitinova EA, Ivanova EV, et al. Evolution of hormonal contraception. Medical Council. 2011;(7–8):61–64. EDN: MVAALB

[28] Прилепская В.Н., Межевитинова Е.А., Иванова Е.В., и др. Эволюция гормональной контрацепции // Медицинский совет. 2011. № 7–8. С. 61–64. EDN: MVAALB

[29] Bradley LD, Gueye NA. The medical management of abnormal uterine bleeding in reproductive-aged women. Am J Obstet Gynecol. 2016;214(1):31–44. EDN: WTLZTD doi: 10.1016/j.ajog.2015.07.044

[30] Bradley L.D., Gueye N.-A. The medical management of abnormal uterine bleeding in reproductive-aged women // Am J Obstet Gynecol. 2016. Vol. 214, N 1. P. 31–44. EDN: WTLZTD doi: 10.1016/j.ajog.2015.07.044

[31] Lethaby A, Wise MR, Weterings MA, et al. Combined hormonal contraceptives for heavy menstrual bleeding. Cochrane Database System Rev. 2019;2(2):CD000154. EDN: LHJHXT doi: 10.1002/14651858.CD000154.pub3

[32] Lethaby A., Wise M.R., Weterings M.A., et al. Combined hormonal contraceptives for heavy menstrual bleeding // Cochrane Database System Rev. 2019. Vol. 2, N 2. ID: CD000154. EDN: LHJHXT doi: 10.1002/14651858.CD000154.pub3

[33] Fraser IS, Jensen JT. Effective treatment of heavy and/or prolonged menstrual bleeding with an oral contraceptive containing estradiol valerate and dienogest: a randomized, double-blind phase III trial. Hum Reprod. 2011;26(10):2698–2708. doi: 10.1093/humrep/der224

[34] Fraser I.S., Jensen J.T. Effective treatment of heavy and/or prolonged menstrual bleeding with an oral contraceptive containing estradiol valerate and dienogest: a randomized, double-blind phase III trial // Hum Reprod. 2011. Vol. 26, N 10. P. 2698–2708. doi: 10.1093/humrep/der224

[35] Jensen JT, Parke S, Mellinger U. Effective treatment of heavy menstrual bleeding with estradiol valerate and dienogest: a randomized controlled trial. Obstet Gynecol. 2011;117(4):777–787. doi: 10.1097/AOG.0b013e3182118ac3

[36] Jensen J.T., Parke S., Mellinger U. Effective treatment of heavy menstrual bleeding with estradiol valerate and dienogest: a randomized controlled trial // Obstet Gynecol. 2011. Vol. 117, N 4. P. 777–787. doi: 10.1097/AOG.0b013e3182118ac3

[37] Yu Q, Zhou Y, Suturina L, et al. Efficacy and Safety of estradiol valerate/dienogest for the management of heavy menstrual bleeding: a multicenter, double-blind, randomized, placebo-controlled, phase III clinical trial. J Womens Health (Larchmt). 2018;27(10):1225–1232. EDN: ODSCZM doi: 10.1089/jwh.2017.6522

[38] Yu Q., Zhou Y., Suturina L., et al. Efficacy and safety of estradiol valerate/dienogest for the management of heavy menstrual bleeding: a multicenter, double-blind, randomized, placebo-controlled, phase III clinical trial // J Womens Health (Larchmt). 2018. Vol. 27, N 10. P. 1225–1232. EDN: ODSCZM doi: 10.1089/jwh.2017.6522

[39] Qlaira. Instructions for use. In: Vidal [Internet]. (In Russ.) [cited 2024 Sep 12] Available from: https://www.vidal.ru/drugs/qlaira__30035

[40] Клайра. Инструкция по применению. В: Видаль [Internet]. Режим доступа: https://www.vidal.ru/drugs/qlaira__30035. Дата обращения: 12.09.2024.

[41] Schroll JB, Black AY, Farquhar C, et al. Combined oral contraceptive pill for primary dysmenorrhea. Cochrane Database System Rev. 2023;7(7):CD002120. EDN: XTEWTS doi: 10.1002/14651858.CD002120.pub4

[42] Schroll J.B., Black A.Y., Farquhar C., et al. Combined oral contraceptive pill for primary dysmenorrhea // Cochrane Database System Rev. 2023. Vol. 7, N 7. ID: CD002120. EDN: XTEWTS doi: 10.1002/14651858.CD002120.pub4

[43] Lindh I, Ellsrom AA, Milsom I. The effect of combined oral contraceptives and age on dysmenorrhoea: an epidemiological study. Hum Reprod. 2012;27(3):676–682. doi: 10.1093/humrep/der417

[44] Lindh I., Ellsrom A.A., Milsom I. The effect of combined oral contraceptives and age on dysmenorrhoea: an epidemiological study // Hum Reprod. 2012. Vol. 27, N 3. P. 676–682. doi: 10.1093/humrep/der417

[45] Genazzani AR, Fidecicchi T, Arduini D, et al. Hormonal and natural contraceptives: a review on efficacy and risks of different methods for an informed choice. Gynecol Endocrinol. 2023;39(1):12247093. EDN: ENUXQX doi: 10.1080/09513590.2023.2247093

[46] Genazzani A.R., Fidecicchi T., Arduini D., et al. Hormonal and natural contraceptives: a review on efficacy and risks of different methods for an informed choice // Gynecol Endocrinol. 2023. Vol. 39, N 1. ID: 12247093. EDN: ENUXQX doi: 10.1080/09513590.2023.2247093

[47] Lopez LM, Grimes DA, Schulz KF. Steroidal contraceptives: effect on carbohydrate metabolism in women without diabetes mellitus. Cochrane Database System Rev. 2019;11:CD00133. doi: 10.1002/14651858.CD006133.pub5

[48] Lopez L.M., Grimes D.A., Schulz K.F. Steroidal contraceptives: effect on carbohydrate metabolism in women without diabetes mellitus // Cochrane Database System Rev. 2012. N 4. ID: CD006133. doi: 10.1002/14651858.CD006133.pub5

[49] Benagiano G, Primiero FM, Farris M. Clinical profile of contraceptive progestins. Eur J Contracept Reprod Health Care. 2004;9(3):182–193. doi: 10.1080/13625180400007736

[50] Benagiano G., Primiero F.M., Farris M. Clinical profile of contraceptive progestins // Eur J Contracept Reprod Health Care. 2004. Vol. 9, N 3. P. 182–193. doi: 10.1080/13625180400007736

[51] Rubanenko OA, Kirichenko NA, Fatenkov OV, et al. Correlation between lipid, hemostatic indicators and stenosis of brachiocephalic arteries in patients with a very high risk of cardiovascular death. Far East Medical Journal. 2016;(1):6–10. EDN: VUWIFX

[52] Рубаненко О.А., Кириченко Н.А., Фатенков О.В., и др. Взаимосвязь показателей липидного обмена, системы гемостаза и стенозов брахиоцефальных артерий у пациентов очень высокого риска смерти от сердечно-сосудистых заболеваний // Дальневосточный медицинский журнал. 2016. № 1. С. 6–10. EDN: VUWIFX

[53] Barcellona D, Grandone E, Marongiu F. Hormones and thrombosis: the dark side of the moon. Blood Transfus. 2024;22(1):46–54. doi: 10.2450/BloodTransfus.535

[54] Barcellona D., Grandone E., Marongiu F. Hormones and thrombosis: the dark side of the moon // Blood Transfus. 2024. Vol. 22, N 1. P. 46–54. doi: 10.2450/BloodTransfus.535

RIGHTS & PERMISSIONS

Eсо-Vector