Uticaj terapije estroprogestagenima u menopauzi na insulinsku senzitivnost i metabolizam lipida

Abstract

Uvod. Incidenca KVB kod žena se značajno povećava posle 50. godine a jedan od mogućih krivaca je i menopauza, koju prati pad vrednosti estrogena, što može biti upleteno u razloge brojnih metaboličkih poremećaja. Promena u distribuciji masnog tkiva, progresivan pad insulinske senzitivnosti praćen povećanom endogenom sekrecijom insulina, značajno povećanje ili smanjenje nivoa nekih lipida i lipoproteina u menopauzi prediktori su razvoja ateroskleroze i KVB. Hormonska terapija u menopauzi (HTM) ima značajan uticaj na metaboličke faktore rizika za razvoj KVB. Dokazano je blagotvorno dejstvo estrogena na metabolizam glukoze i insulina. Primena estrogena smanjuje LDL i Lp(a), uz povećanje triglicerida i HDL, što zavisi od doze i puta primene leka. Istovremena primena progestagena, zavisno od vrste, može imati različite efekte na lipide. Cilj rada je bio ispitivanje uticaja terapije estroprogestagenima na insulinsku senzitivnost i metabolizam lipida žena u menopauzi, zavisno od puta primene leka. Metode. Istraživanje je sprovedeno po tipu Retrospektivne Kliničke Interventne kontrolisane studije paralelnih grupa. Obuhvatilo je 64 žene u menopauzi podeljenih u tri grupe: grupa 1 (N=22), na oralnim estroprogestagenima (2 mg estradiola u obliku estradiol hemihidrata; 2 mg estradiola i 1 mg noretisteron acetata; 1 mg estradiola), grupa 2 (N=17), na transdermalnim estroproge-stagenskim flasterima (50 μg 17-β estradiola i 250 μg noretindron acetata dnevno) i grupa 3 (N=25), na intramuskularnim estroprogestagenima (4 mg estradiol valerata i 200 mg prasteron enantata). Za procenu lipidnog metaboličkog profila određivani su: ukupni holesterol (HOL) (mmol/L), HDL (mmol/L), LDL (mmo/L), TG (mmol/L), Lp(a) (g/L), apolipoprotein A (Apo-A) (g/L), apolipoprotein B (Apo-B) (g/L). Za ispitivanje isnulinske senzitivnosti korišćen je standardni dvočasovni test oralne tolerancije glukoze (OGTT-Oral Glucose Tolerance Test) sa 75 gr. glukoze. Insulinska rezistencija je određivana HOMA (Homeostasis Model Assessment) metodom, Matsuda indeksom insulinske senzitivnosti kao i površinom ispod krive (AUC- Area Under the Curve) insulinemija i ispod krive glikemija (izračunavano kao površina trapezoida). Hormonski status definisan je vrednostima folikulostimulišućeg hormona (FSH) (IU/L), luteinizujućeg hormona (LH) (IU/L), estradiola (E2) (pmol/L), progesterona (P) (nmol/L), testosterona (T) (nmol/L), vezujućeg globulina za polne hormone (SHBG) (nmol/L), dehidroepiandrosteron-sulfata (DHEAS) (μmol/L), prolaktina (PRL)(mIU/L) i tireostimulišućeg hormona (TSH) (mIU/L)...

The incidence of CVD in women is significantly increased after 50 years, and one of the possible factors is menopause, which is followed by a decline in estrogen values, which itself can be involved in the occurrence of numerous metabolic disorders. A change in the distribution of fatty tissue, a progressive decline in insulin sensitivity followed by increased endogenous insulin secretion, a significant increase or decrease in levels of some lipids and lipoproteins in menopause are the predictors for the development of atherosclerosis and CVD. Menopausal hormone therapy (MHT) has a significant effect on metabolic risk factors for the development of CVD. The beneficial effect of estrogen on the metabolism of glucose and insulin has been demonstrated. The use of estrogen reduces LDL and Lp (a), and increases triglycerides and HDL, which depends on the dose and route of administration of the drug. Simultaneous application of progestagen, depending on the type, may have different effects on lipids. The aim of the study was to examine the effect of estroprogestagen therapy on insulin sensitivity and lipid metabolism in menopausal women, depending on the route of administration of the drug. Methods. The study was conducted as Retrospective Clinical Interventional Controlled Study of Parallel Groups. The study included 64 women in menopause divided into three groups: group 1 (N=22), on oral oestroprogestagens (2mg estradiol in the form of estradiol hemihydrate; 2 mg estradiol and 1 mg norethisterone acetate; 1 mg of estradiol), group 2 (N=17) on transdermal estroprogestagen patch (50μg of 17-β estradiol and 250 μg of norethindron acetate per day) and group 3 (N=25), on intramuscular estroprogestagens (4mg estradiol valerate and 200mg of prasterone enanthate). To evaluate the lipid metabolic profile we measured total cholesterol (HOL) (mmol/L), HDL (mmol/L), LDL (mmo/L), TG (mmol/L), Lp(a) (g/L) apolipoprotein A (Apo-A) (g/L), apolipoprotein B (Apo-B) (g/L)...