Modern Nonhormonal POSSIBILITY of POLYCYSTIC OVARY SYNDROME TREATMENT in Obese Women

Статья: Профарма_медред Медред: 07.11.2013 Литред: 7.11.2013 Верстка:

MODERN NONHORMONAL POSSIBILITY OF POLYCYSTIC OVARY SYNDROME TREATMENT IN OBESE WOMEN

T.F. Tatarchuk, MD, professor, corresponding member of NAMS of Ukraine, Deputy Director for Research Work, Chief of the Endocrine Gynecology Department, Institute of Pediatrics, Obstetrics and Gynecology, NAMS of Ukraine I.Y. Ganji, Institute of Pediatrics, Obstetrics and Gynecology, NAMS of Ukraine N.Y. Pedachenko, Institute of Pediatrics, Obstetrics and Gynecology, NAMS of Ukraine I.N. Kapshuk, Endocrine Gynecology Department, Institute of Pediatrics, Obstetrics and Gynecology, NAMS of Ukraine

Polycystic ovary syndrome (PCOS) is one of the most urgent problems of modern gynecology. PCOS case more than half of all cases of endocrine infertility (50-75%). PCOS is diagnosed in 5-16% of women of reproductive age [1-3]. The main clinical manifestations of PCOS are menstrual disorders, anovulatory infertility and androgen skin disorders (hirsutism, acne), and in 50% patients - obesity, manifested at the age of menarche [1, 4-6]. PCOS is a systemic illness in which violated all parts of the endocrine system, not just the ovaries. For a long time treatment of PCOS was aimed at restoring menstrual and generative function [4, 9]. Today more and more attention is paid to the comprehensive approach to the treatment of disorders in patients with PCOS, taking into account their age, reproductive plans and hormonal levels. Combined oral contraceptives (COCs) are extensive use during the last decade [8]. However, suppression of ovarian hormones in young women is not always desirable. In connection with the foregoing, the studies of opportunities nonhormonal treatment of PCOS continue. In recent years is widely studied the use in the treatment of PCOS naturally occurring drugs that regulate blood flow, trophic, metabolic and functional state of the reproductive endocrine system. The advantage of these drugs is low toxicity and the possibility of long-term use without the risk of serious adverse reactions. In this context, is interested a non-hormonal herbal medicine Tazalok (pharmaceutical company "ProFarma") with complex action, defined as synergistic effect of biologically active substances that are part of it. The drug causes the smooth development and normalization of the ratio of gonadotropin-releasing hormone, regulates the second phase of the menstrual cycle, and eliminates the imbalance between estradiol and progesterone. The indications for the drug Tazalok are menstrual disorders, premenstrual syndrome, algomenorrhea, dysmenorrhea, menopausal disorders. The drug is also recommended in the adjuvant therapy of PCOS. The aim of our study was to investigate the possibility of using multicomponent herbal drug in the treatment of PCOS.

STUDY MATERIALS AND METHODS To achieve this goal we examined 120 women with PCOS on a background of excessive weight gain and obesity at age 18-25 years (study group) and 42 gynecological and somatically healthy women of the same age (control group). There were such criteria for inclusion in the study: PCOS with the presence of ovarian enlargement and oligo/anovulation and normal levels of ovarian androgens, body mass index (BMI) ≥ 25 kg/m2. All patients of the main group by sampling random were divided into 4 groups according to the prescribed therapy. In the 1st subgroup of women treated with metformin and Tazalok, 2nd - metformin and a basic therapy that includes salts of magnesium, folic acid, vitamin B and vitamin D; 3rd - metformin and Tazalok base complex, in 4th - COC with folic acid. In addition, all patients were given dietary advice on nutrition and physical activity. Therapy was performed within 6 months with examination at the end of treatment (6 months after the first examination) and after 3 months (9 months after the first examination). Hormonal studies were performed: levels of luteinizing hormone (LH), follicle stimulating hormone (FSH), thyroid stimulating hormone, prolactin, T4, estradiol, progesterone, androstenedione, 17-hydroxyprogesterone, testosterone, insulin, anti-mulerian hormone (AMH), dehydroepiandrosterone sulfate (DHEA-S), LH/FSH ratio, free androgen index were estimated. Biochemical studies included the determination of glucose, cholesterol, LDL and HDL, triglycerides. For statistical analyses were used Student's criterion and Pearson criterion χ2. The difference was considered reliable when p < 0,05.

RESULTS BMI in all experimental subgroups was significantly higher than that of the control (p < 0.05). After 6 months of treatment was a tendency to it decrease in 1, 2 and 3 subgroups, but the difference was statistically significant only in patients treated with metformin and developed complex (13.5%, p < 0.05). Achieved positive changes remained after withdraw of treatment. In the 4 subgroup there was not significant change in BMI (pn> 0.05). Significant increase of homocysteine compared with a group of healthy women and reducing the amount of magnesium and 25-hydroxyvitamin D was observed only in the Presence of hirsutism rating on a Ferriman–Gallwey score scale in main group was at transient values in all subgroups (9,44 ± 0,14; 8,67 ± 0,12; 8,22 ± 0,10 and 10,73 ± 0,11 points, respectively in subgroups 1, 2, 3 and 4). They are significantly higher than in controls (3,55 ± 0,12 points) (p < 0,05) and did not change in the dynamics of treatment and follow-up (p > 0.05). In patients in 2, 3 and 4 subgroups it was registered probable reduction in the incidence of acne after the treatment of 2.33, 3.14 and 2.67 times respectively (p < 0,05). After 3 months of observation achieved positive trend continued. In subgroup 1 probable change have occurred (p> 0.05). In the treatment significantly increased the number of women who had regular menstrual cycles (3 times in subgroup 1, p < 0,05; 4.6 times in subgroup 2, p < 0,05; 5,25 times in subgroup 3, p < 0 ,05, 10 times in subgroup 4, p < 0,05). 3 months after end of the treatment improvement remained statistically in all subgroups (p < 0,05). Thus, analysis of clinical data showed that the treatment of women with PCOS on a background of excessive body weight and normal levels of testosterone did not affect the degree of hair growth, but led to improvement of the skin and menstrual regularity. The maximum positive effect was registered in the complex taking metformin, basic complex and Tazalok. LH levels significantly decreased in subgroups 1 and 3 (p < 0,05) after 6 months of treatment. These changes remained after 3 months follow-up. The concentration of FSH fluctuated during treatment, but these changes were not statistically significant (p > 0.05). LH/FSH ratio in patients taking metformin and developed therapy decreased in 1.79 and 1.56 times respectively (p < 0,05). These positive trends continued even after end of the treatment. There was significant difference of the concentration of prolactin, thyroid stimulating hormone, thyroxine and triiodthyronine between subgroups in the dynamics of treatment (p > 0.05). During treatment and follow-up period estradiol levels decreased slightly in women of all subgroups, but significantly (p < 0,05) was changes after 6 months of treatment only in patients who received COC (from 76,53 ± 3,41 to 35.24 ± 4,37 pg / ml). Progesterone levels significantly decreased by 1.3 times (p < 0,05) in patients receiving COC and after treatment returned to the original low value. Pronounced positive dynamics was registered in subgroup 3, in which the concentration of progesterone increased in 2.2 times (p < 0,05). After 3 months after treatment it decreased slightly. It should be noted that despite the positive trend, progesterone levels did not reach values comparable with healthy women. Testosterone and DHEA-S were within reference values in all subgroups. The AMH level in subgroups was significantly higher at baseline (5,83 ± 0,62; 6,19 ± 0,41; 5,67 ± 0,34 and 6,43 ± 0,26 ng / ml) than in gynecological healthy women of the same age (2,17 ± 0,43 ng / ml) (p < 0,05). After 6 months of treatment in subgroups 1, 3 and 4, it significantly decreased (4,16 ± 0,41; 3,88 ± 0,42; 3,34 ± 0,56 ng / ml, respectively) (p < 0,05) but remained higher than that of the control subgroup (p < 0,05). It should be noted that 3 months after treatment this result remained in subgroups 1 and 3 (4,78 ± 0,29 and 4,11 ± 0,37 ng / ml) (p < 0,05), while in subgroup 4 it almost returned to initial values (6,21 ± 0,42 ng / ml, p > 0.05), and did not significantly change in the dynamics in subgroup 2 it (6,31 ± 0,25 and 6 29 ± 0,18 ng / ml, respectively) (p > 0.05). Cortisol concentrations showed a significant reduction in sub-groups 2 and 3 after 6 months (161,43 ± 5,51 and 146,17 ± 4,26 nmol / l respectively, with initial values of 224,36 ± 4,83 and 217,51 ± 6,04 nmol / L) (p < 0,05). Assessment of adipocytokine metabolism showed the presence hiperleptynemia in patients with PCOS and excess body weight (792,168 ± 71,26 vs. 352,11 ± 82,37 pg / ml in the control group) (p < 0,05). The level of adiponectin was 1.37 times lower in women main group (12,69 ± 1,22 vs16,20 ± 1,75 mg / ml). Resistin and interleukin-6 concentrations did not show significant differences between the study groups. Thus, the study of hormonal homeostasis showed that during developed treatment in women with overweight and normal testosterone levels are not registered significant changes of thyroid, androgen hormones, whereas metformin with Tazalok use decreased levels of LH and AMH, basic complex - cortisol and AMH; complex using drugs - decreased LH, AMH, cortisol and progesterone increased, while taking COCs - decreased AMH. Determination of carbohydrate metabolism parameters showed no significant changes in the dynamics of glucose concentration (p > 0.05). At the same time it was registered probable differences in the levels of insulin and insulin resistance indices between subgroups during treatment and follow- up – before treatment all women had elevated insulin levels more than 2-fold compared with control (p < 0,05), after 6 months of treatment in subgroups 1 and 3 it concentration decrease of 2.17 and 2.11 times (p < 0,05), these results saved during the observation, there was lack of dynamics in groups 1 and 4 ( p> 0, 05). Implementation of the proposed measures resulted in changes lipid metabolism. Thus, cholesterol at beginning of treatment was within the reference values, but higher than that of healthy women on average 1.5 times (p < 0,05). After 6 months therapy its concentration decreased significantly in subgroups 2 and 3 (1.5 times, p < 0.05), whereas in the subgroups 1 and 4 did not change significantly (p > 0.05). It should be noted that after the end of treatment achieved positive changes are saved. Pre-treatment triglyceride levels were almost twice higher than in the control group (p < 0,05); during treatment triglyceride levels decreased 1.61 and 1.65 times in subgroups 2 and 3 (p < 0,05) with saving of this result at follow-up, in subgroups 1 and 4 triglyceride levels did not change (p > 0.05). The concentration of cholesterol was on average 1.5 times higher than that of the control (p < 0,05) and significantly decreased in patients who received developed optimal complex - in 1.2 times with respect to the initial state (p < 0,05). Positive results remained after 3 months follow-up. In subgroups 1 and 4 there was not changes of LDL level (p > 0.05). The content of HDL did not change significantly during the study in all subgroups (p > 0.05).

CONCLUSIONS Evaluating the effectiveness of the developed approach has shown that the most effective is to use a holistic approach to treatment, which can influence the pathogenesis and leads to an increase in the frequency of regular menstrual cycles normalize hormonal homeostasis, including AMH and cortisol. Using this approach it is possible to normalize the function of adipose tissue, and improve the performance of adipose tissue hormones and to improve their relationship with the pituitary-adrenal and pituitary-ovarian system. It should be noted that COC use in patients with obesity and normal androgen level leads only to some cosmetic effect and the regulation of the cycle for the period of treatment, without affecting or impairing the other types of metabolism, leading to destabilization, deepening of existing violations and the transition from functional into organic changes.

СОВРЕМЕННЫЕ ВОЗМОЖНОСТИ НЕГОРМОНАЛЬНОГО ЛЕЧЕНИЯ СИНДРОМА ПОЛИКИСТОЗНЫХ ЯИЧНИКОВ У ЖЕНЩИН С ОЖИРЕНИЕМ Т.Ф. Татарчук, д. мед. н., профессор, член-корр. НАМН Украины, заместитель директора по научной работе, зав. отделением эндокринной гинекологии Института педиатрии, акушерства и гинекологии НАМН Украины И.Ю. Ганжий, Институт педиатрии, акушерства и гинекологии НАМН Украины Н.Ю. Педаченко, Институт педиатрии, акушерства и гинекологии НАМН Украины И.Н. Капшук, отделение эндокринной гинекологии Института педиатрии, акушерства и гинекологии НАМН Украины

Цель исследования – изучить возможности использования поликомпонентным растительным препаратом в комплексном лечении синдрома поликистозных яичников (СПКЯ) у женщин с ожирением и нормальным уровнем яичниковых андрогенов. Было обследовано 120 пациенток с СПКЯ и 30 условно соматически и гинекологически здоровых женщин. Изучен анамнез, антропометрические данные, гормональный, липидный, карбогидратный, адипоцитокиновый обмены, уровень 25-гидрокивитамина D до и в процессе лечения и наблюдения. Все обследованные были разделены на подгруппы в зависимости от использования того или иного компонента лечебного комплекса. Авторы показали, что использование разработанного подхода с включением в схему лечения поликомпонентного растительного препарата позволило нормализовать функцию жировой ткани и улучшить ее взаимосвязь с гипофизарно-надпочечниковой и гипофизарно- яичниковой системами, нормализовать менструальный цикл. Использование КОК у пациенток с ожирением и нормоандрогенией дало лишь некоторый косметический эффект и регуляцию цикла на период приема, не влияя или ухудшая состояние других видов обмена, что приводит к дестабилизации, углубление существующих нарушений и переходу изменений с функционального на органический уровень.

Ключевые слова: синдром поликистозных яичников, ожирение, адипоцитокины, лечение.

MODERN NONHORMONAL POSSIBILITY OF POLYCYSTIC OVARY SYNDROME TREATMENT IN OBESE WOMEN

T.F. Tatarchuk, MD, professor, corresponding member of NAMS of Ukraine, Deputy Director for Research Work, Chief of the Endocrine Gynecology Department, Institute of Pediatrics, Obstetrics and Gynecology, NAMS of Ukraine I.Y. Ganji, Institute of Pediatrics, Obstetrics and Gynecology, NAMS of Ukraine N.Y. Pedachenko, Institute of Pediatrics, Obstetrics and Gynecology, NAMS of Ukraine I.N. Kapshuk, Endocrine Gynecology Department, Institute of Pediatrics, Obstetrics and Gynecology, NAMS of Ukraine

The aim of the study was to explore the use of multicomponent herbal preparation in treatment of polycystic ovary syndrome (PCOS) in women with obesity and normal levels of ovarian androgens. We examined 120 patients with PCOS and 30 healthy women. Anamnesis, anthropometric data, hormonal, lipid, carbohydrate, adipoсytokinе homeostasis, the level of 25-OH-Vit D before and during treatment and observation were studied. All subjects were divided into subgroups according to the use of a component of a treatment complex. The authors found that the use of the developed approach with the inclusion in the scheme of treatment multicomponent herbal preparation gives possible normalize the function of adipose tissue and improve its relationship with the pituitary-adrenal and pituitar-ovarian systems, normalize the menstrual cycle. COC use in patients with obesity and normal androgen level leads only to some cosmetic effect and the regulation of the cycle for the period of treatment, without affecting or impairing the other types of metabolism, leading to destabilization, deepening of existing violations and the transition from functional into organic changes. Key words: polycystic ovary syndrome, obesity, adipocytokines, treatment.

REFERENCES/ЛІТЕРАТУРА 1. Геворкян М.А. Клиника, диагностика и лечение синдрома поликистозных яичников / М.А. Геворкян, И.Б. Манухин, Л.Б. Студеная [и др.] // ЖРОАГ. – 2008, № 4.– С. 3–20. Gevorgyan MA Clinic, diagnosis and treatment of polycystic ovary syndrome / MA Gevorgyan, IB Manukhin, LB Studenaya [etc.] // ZHROAG. – 2008, № 4. – P. 3–20. 2. Глухов Н.В. Заболевания, ассоциированные с синдромом поликистозных яичников и метаболическим синдромом / Н.В. Глухов, С.Ю. Чубриева, Н.А. Беляков // Эфферентная терапия. – 2007. – ТОМ 13. – № 1. – С.17–19. Gluhov NV Diseases associated with polycystic ovary syndrome and metabolic syndrome / NV Gluhov, SJ Chubrieva, NA Belyakov // Efferent Therapy. – 2007. – Vol.13. – № 1. – P. 17–19. 3. Mukherjee S Polycystic ovary syndrome. Review/ Mukherjee S, Maitra A// Indian J Med Res. – 2010. – Vol.131. – P. 743–760. 4. Грищенко В.И. Синдром поликистозных яичников как причина эндокринного бесплодия/ В.И. Грищенко, Н.Г. Грищенко, И.В. Загребельная [и др.] // Медицинские аспекты здоровья женщины. – 2010. – № 1 (28). – С. 5–12. Grishchenko VI Polycystic ovary syndrome as a cause of endocrine infertility / Grishchenko VI, Grishchenko NG, Zagrebelnaya IV [etc.] // Medical Aspects of Women’s Health. – 2010. – № 1 (28.) – P. 5–12. 5. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group 2004 Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS)//Hum Reprod. – 2004. – Vol.19. – P.41-47. 6. Гопчук Е.Н. Оптимизация диагностики синдрома поликистозных яичников / Е.Н. Гопчук // Збірник наукових праць Асоціації акушерів-гінеколгів України. – К.: Інтермед, 2011. – С. 189-194. Gopchuk EN Optimizing the diagnosis of polycystic ovary syndrome / E. Gopchuk // Proceedings of the Association of Obstetricians of Ukraine. – K.: Іntermed, 2011. – P. 189–194. 7. Дедов И.И. Эндокринология / Дедов И.И., Мельниченко Г.А. – М.: Триада-Х, 2008. – 289 с. Dedov II Endocrinology / Dedov II, GA Melnichenko. – Moscow: Triada-X, 2008. – 289 p. 8. Науменко В.Г. Гиперандрогенные состояния / Науменко В.Г. // Медицинские аспекты здоровья женщины. – 2011. – № 1 (40). – С. 5–102. Naumenko VG Hyperandrogenism status / VG Naumenko // Medical Aspects of Women’s Health. – 2011. – № 1 (40). – P. 5–102. 9. Зыкова Т.Д. Метаболические особенности синдрома поликистозных яичников у женщин с нормальной и избыточной массой тела / Зыкова Т.Д., Стрелкова А.В., Савенко Б.А., Мельниченко Г.А. // Сахарный диабет. – 2003. – № 1(18). – С.16-21. Zykova TD Metabolic features of polycystic ovary syndrome in women with normal and overweight / TD Zykova, AV Strelkova, BA Savenko, GA Melnichenko // Diabetes. – 2003. – № 1 (18). – P. 16–21. 10. Татарчук Т.Ф. Жировая ткань и репродуктивная система женщины / Татарчук Т.Ф., Косей Н.В., Ганжий И.Ю. // Здоров’я України. – 2008. – № 24/1. – С. 14–16. Tatarchuk TF Adipose tissue and the reproductive system of women / Tatarchuk TF, Cossey NV, Ganji IY // Health Protection of Ukraine. – 2008. – № 24/1. – P. 14–16. 11. Шилин Д.Е. Синдром поликистозных яичников Международный диагностический консенсус (2003 г.) и современная идеология терапии / Шилин Д.Е.// Consilium Medicum. – 2004. – Т. 06, № 9. – С. 27–31. Shilin DE Polycystic Ovary Syndrome Diagnostic International Consensus (2003) and the modern ideology therapy / DE Shilin // Consilium Medicum. – 2004. – T. 06, № 9. – P. 27–31. 12. Светлаков А.В. Лептин и липидный спектр крови у женщин с разными типами ожирения / Светлаков А.В., Яманова М.В., Филиппов О.С., Махалова Н.А. // Проблемы репродукции. – 2001. – № 6. – С. 29–32. Svetlakov AV Leptin and blood lipid profile in women with different types of obesity / Svetlakov AV, Yamanova MV, Filippov OS, Mahalova NA // Problems of Reproduction. – 2001. – № 6. – P. 29–32. 13. Коваль С.Н. Гормон жировой ткани адипонектин и его роль в патогенезе метаболического синдрома и сердечно-сосудистых. Гипоадипонектинемия как терапевтическая мишень (обзор литературы) / Коваль С.Н., Снегурская И.А. // Журнал НАМН України. – 2011. – Т. 17, № 2. – С. 174–185. Koval SN Adipose tissue adiponectin hormone and its role in the pathogenesis of the metabolic syndrome and cardiovascular diseases. Hypoadiponectinemia as a therapeutic target (review) / Koval SN, Snegursky IA // Journal of NAMS of Ukraine. – 2011. – V. 17, № 2. – P. 174–185. 14. Lindsay RS Adiponectin and development of type 2 diabetes in the Pima Indian population / Lindsay RS, Funahashi T, Hanson RL [et al.] // Lancet. –2002. – Vol. 360. – P.57–58. 15. Iniguez G Adiponectin levels in the ﬁrst two years of life in a prospective cohort: relations with weight gain, leptin levels and insulin sensitivity / Iniguez G, Soto N, Avila A [et al.] // J. Clin. Endocrinol. Metab. – 2004. – Vol. 89. – P. 5500–5503. 16. Ducluzeau PH Glucose-to-insulin ratio rather than sex hormone-binding globulin and adiponectin levels is the best predictor of insulin resistance in nonobese women with polycystic ovary syndrome / Ducluzeau PH, Cousin P, Malvoisin E [et al.] // Ibid. – 2003. – Vol. 88. – P. 3626–3631. 17. Yilmaz M Serum resistin and adiponectin levels in women with polycystic ovary syndrome / Yilmaz M, Bukan N, Dtvirci H [et al.] // International Society of Gynecological Endocrinology. – 2009. – №. 32/4. – P. 68–74. 18. Дедов И.И. Синдром поликистозных яичников и метаболический синдром / И.И. Дедов, С.А. Бутрова // Ожирение и метаболизм. – 2006. – № 1. – С. 30–40. Dedov II Polycystic ovary syndrome and metabolic syndrome / Dedov II, Butrova SA // Obesity and Metabolism. – 2006. – № 1. – P. 30–40.