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  • br Introduction Oral contraceptives OCs are the most commonl


    Introduction Oral contraceptives (OCs) are the most commonly used medication for contraception all over the world and are also used in the treatment of menstrual disturbances and hyperandrogenism in women with polycystic ovary syndrome [1]. The impact of OC steroids on cardiovascular pathophysiology remains an important debate due to the popularity of their choice coupled with the adverse cardiometabolic effects. The use may have negative effects on glucose tolerance and the lipid profile, promoting the risk of type 2 diabetes and/or cardiovascular disease [2], [3], [4], [5], [6]. However, these effects may depend on the dose of estrogen, as well as the dose and/or type of progestogen [7], [8]. The initial OCs were introduced in the early 1960s, after which myocardial infarction emerged as an adverse effect particularly in users with concomitant cardiovascular risk factors, such as smoking, aging and hypertension [9], [10]. Since the introduction, doses of OC NK 252 have decreased from 150μg in first-generation OCs to 50μg in second-generation OCs and currently, prescribed doses of estrogen (ethinyl estradiol; EE) are ranging from 20μg ‘very low dose’ to 30μg ‘low dose’ [6]. While currently used OC estrogen dosing improves the safety, preventing venous events, it has also been associated with increases in arterial events such as myocardial infarction and stroke [11]. The reduction of estrogen dose in combination with lower progestogen doses appears to have variable effects on blood glucose levels, glucose tolerance and lipid profile. Furthermore, studies on association between OC use and type 2 diabetes have shown conflicting results that may be due to differences in study populations, duration, dosing, and type of OCs used [12]. All hormonal contraceptives contain a progestogen component and are available in a variety of forms: combined OCs (containing both estrogen and progestogen), progestogen-only OCs, injectable progestogens, and progestogen implants. Currently available hormonal contraceptives differ from one another in dose as well as the degree of androgenicity of the progestogen. Early metabolic studies of combined OC suggest that formulations with higher doses of the more androgenic forms of progestogens (such as norgestrel and levonorgestrel) are associated with greater alterations of glucose metabolism [13], [14], [15]. New formulations of OCs, with lower doses of progestogens, have been formulated to minimise these side effects. However, results of studies on low dose formulations and glucose metabolism among non-diabetic users have been conflicting [16], [17]. The atherosclerotic vascular occlusive diseases risk of OC is partly attributed to their adverse effects on lipid and glucose metabolism [18]. It has been demonstrated that impaired fasting blood glucose, impaired glucose tolerance and unfavourable lipid profile are important risk factors for the development of heart disease, and atherogenesis has been reported as the final common pathway [19]. The abnormal lipid profile caused by OC also appears to be dependent on dose and/or type of OC [14], [20]. The present study, therefore, was designed to investigate in a well-controlled female rat model whether or not glucose tolerance and plasma lipid profile associated with OC use are estrogenic-, progestogenic- or dose-dependent.
    Materials and methods
    Results There was no significant difference in body weight and fasting blood glucose among the groups before and after the treatment period (Table 1). Body weight gain seemed to be attenuated significantly only in LOC-treated group (Table 1). There was no significant difference in plasma TC, LDL-cholesterol levels, and atherogenic indices (TC/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol) among the experimental groups (Table 2). When compared with vehicle-treated group, both HCOC and LCOC groups had significantly higher plasma levels of TG. The increases in TG levels NK 252 in both groups were comparable (Table 2). There was a significant decrease in plasma HDL cholesterol levels in HCOC group compared with other groups (Table 2). In comparison to vehicle-treated group, only HCOC group had a significantly higher mean values of blood glucose level after 90min of oral glucose load and AUC (Fig. 1, Fig. 2).