- Email: [email protected]
Evaluation of lipid profile in adolescents during long-term use of combined oral hormonal contraceptives
Contraception 71 (2005) 118 – 121
Original research article
Evaluation of lipid profile in adolescents during long-term use of combined oral hormonal contraceptives Christina Aparecida Falbo Guazzellia,*, Prescilla Chow Lindseya, Fabio Fernando de Arau´joa, Ma´rcia Barbieria, Carlos Alberto Pettab, Jose Mendes Aldrighic a
Family Planning Clinic, Department of Obstetrics and Gynecology, Universidade Federal de Sa˜o Paulo (UNIFESP), Sa˜o Paulo CEP 09090050, Brazil b Human Reproduction Unit, Department of Obstetrics and Gynecology, School of Medicine, Universidade Estadual de Campinas (UNICAMP), 13083530 Campinas, Brazil c Department of Maternal Health, School of Public Health, University of Sa˜o Paulo, Sa˜o Paulo 05663030, Brazil Received 24 October 2003; revised 29 July 2004; accepted 2 August 2004
Abstract The study evaluated the effects of the long-term use of a combined oral hormonal contraceptive containing 30 Ag ethinyl estradiol and 75 Ag gestodene in adolescents. Thirty-three volunteers, aged from 14 to 19 years, who used the oral contraceptive for three consecutive years, were studied. Evaluation of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides was made before use and after 1, 2 and 3 years. During the 3-year study period, total cholesterol, HDL-C, LDL-C and triglyceride levels were significantly higher than previous measurements, but average values did not exceed the normal range. Compared to the first year, the second- and third-year cholesterol, HDL-C, LDL-C and triglyceride levels were not significantly different. D 2005 Elsevier Inc. All rights reserved. Keywords: Adolescents; Contraceptives; Hormonal contraceptives; Cholesterol; Triglycerides
1. Introduction
2. Materials and methods
Combined oral contraceptives (COC) are popular among adolescents since they are highly efficient and easy to use. Although the consequences of their use have been extensively reviewed in adult women, there have been few studies involving adolescents. The most feared complications of oral hormonal contraceptives include thromboembolic phenomena and cardiovascular disease [1]. Previous studies have demonstrated that atherosclerosis is a process that begins in young adults and can be accelerated by the presence of risk factors such as smoking, alcohol, obesity and oral hormonal contraceptives [2]. The objective of this study was to evaluate the effects of the long-term use of monophasic combined hormonal oral contraceptives on the lipid metabolism of adolescents.
All adolescents attending the Family Planning Clinic of Sa˜o Paulo Federal University who elected COC as their method of choice were invited to participate in the study. Of the initial 80 participants, 58 completed 1 year of study, 50 completed 2 years and 33 completed 3 years. Therefore, the study population consisted of 33 adolescents who used monophasic oral hormone contraceptive (21 tablets monthly containing gestodene 75 Ag and ethinyl estradiol 30 Ag each) who were prospectively evaluated for 3 years. The study was approved by the Ethics Committee of UNIFESP (Universidade Federal de Sa˜o Paulo) and all participants signed an informed consent form. The exclusion criteria were: WHO medical eligibility criteria categories 3 and 4 [3]; use of an oral hormonal contraceptive in the three previous months prior to entry in the study; concomitant use of medications that might interfere in lipid metabolism (thiazides, corticosteroids, hblockers, cyclosporine); smoking; cholesterol values higher than 199 mg/dL at baseline [4]; hemoglobin lower than 12 g/dL; body mass index (BMI; weight/height2) higher than
* Corresponding author. Tel.: +55 11 557 22605; fax: +55 11 557 22605. E-mail address: [email protected] (C.A.F. Guazzelli). 0010-7824/$ – see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.contraception.2004.08.002
C.A.F. Guazzelli et al. / Contraception 71 (2005) 118–121
119
95th percentile; family history of thromboembolic diseases or myocardial infarct before 50 years of age in men and 60 years in women. All participants were healthy and had normal physical and gynecological exams before starting contraceptive use. These were repeated every 3 months during the 3-year study period. The lipid profile consisted of total cholesterol, highdensity lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides before (T0) and after 1 (T1), 2 (T2) and 3 (T3) years of oral hormonal contraceptive use. The levels of each parameter obtained at baseline were considered as control values for each patient. Total cholesterol values below 199 mg/dL and LDL-C below 129 mg/dL were considered normal and triglyceride levels were classified as adequate when lower than 131 mg/dL [4]. Measurements were made throughout the 3 years of the study, immediately after each sample collection.
Compared to baseline values, total cholesterol levels increased significantly after 1 (T1), 2 (T2) and 3 (T3) years of contraceptive use (Table 1), as did HDL-C values. At baseline, 11 adolescents had HDL-C below 35 mg/dL. After starting contraceptives and throughout the study period, only four measurements were lower than 35 mg/dL. In five adolescents, total cholesterol level rose above normal limits (199 mg/dL) during the 3-year study period. None of these patients had BMI above the 95th percentile. Triglycerides and LDL-C also increased significantly after 1, 2 and 3 years of oral hormonal contraceptive use (Table 1). In the second and third years of the study, cholesterol, HDL-C, LDL-C and triglyceride levels did not differ significantly from those obtained in the first year.
2.1. Laboratory assays
4. Discussion
Enzyme kits and an auto-analyzer were used to determine total cholesterol, HDL-C and triglyceride levels. Cholesterol was measured on supernatant using the ADVIA 1650-Bayer colorimetric enzyme kit. According to solution characteristics, concentrations up to 500 mg/dL were detectable. HDL-C was quantified using the same technique as for cholesterol, after precipitation with dextran sulfate. VLDLC was obtained dividing triglyceride values by 5. This method could be used since triglycerides levels were b 400 mg/dL in all samples.
Atherosclerosis is an important cause of adult mortality and its prevention can be initiated in childhood through adequate evaluation of family history (hypercholesterolemia or early myocardial infarct) and periodic exams of cholesterol levels. Several additional risk factors have been identified, such as smoking, obesity, hypertension, diabetes and high levels of cholesterol [1]. Adolescence is a time of great personal changes and frequently marks the beginning of undesirable habits such as smoking, sedentary lifestyle and improper eating patterns, such as the ingestion of large amounts of food rich in saturated fat. Frequently, it is also the period of sexual initiation, hence the need for contraceptive methods. Adolescents frequently prefer oral hormonal contraceptives because they are highly efficient, reduce dysmenorrhea and improve menstrual cycle control [5]. Consequences of oral contraceptive use have been widely studied in adult women but the adolescent population has been less studied. Therefore, recommendations for the prescription of OC to adolescents are largely based on guidelines originally designed for adult women [6]. In this study, we observed a statistically significant elevation in total cholesterol, HDL-C, LDL-C and triglycerides levels. Although this increase alone may not jeopardize the health of a young adult, it could increase the effect of other risk factors [6].
2.2. Statistical analysis The sample size was calculated as a minimum of 30 patients followed-up for 3 years, with a 90% power to detect differences of 1 standard deviation comparing the four annual averages. Significance was established at 5%. A paired t test was used to compare average values of each variable (total cholesterol, HDL-C, LDL-C and triglycerides). Confidence intervals were set at 95% (c =0.95 or 95%). 3. Results The mean age at entry was 16.6 years and average age at menarche was 12.4 years with a standard error of 0.2 years. The mean age at first intercourse was 15.4 and 72.7% of the patients had no previous pregnancies.
Table 1 Lipid profile of 33 adolescents using oral hormonal contraceptives for 3 years Parameter
Baseline (T0)
After 1 year (T1)
After 2 years (T2)
After 3 years (T3)
Cholesterol HDL-C LDL-C Triglycerides
148.06F23.78 40.24F10.07 91.7F19.15 80.52F32.34
178.82F36.36* 47.97F10.51* 111.21F30.08* 98.30F40.54**
184.06F35.05* 50.85F10.6* 113.55F32.35* 98.33F43.61**
184.15F36.35* 53.94F14.59* 111.39F37.51** 99.45F44.74**
* p b .001 paired t test in comparison with baseline values. ** p b .05.
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C.A.F. Guazzelli et al. / Contraception 71 (2005) 118–121
In adolescence, interaction of risk factors is common, especially smoking and obesity. Since up to 30 –35% of adolescents smoke and this habit could modify their lipid profile, we decided to exclude all smokers from this study [7,8]. Obesity, a frequent condition in adolescents, has been associated with elevated levels of triglycerides and total cholesterol and a decrease in HDL-C [9]. These lipoprotein modifications may predispose to lipid deposits in the aorta and coronaries, initiating atherosclerosis [10]. It should be noted that five young women who showed persistent and abnormal increase in cholesterol levels throughout the 3-year study period presented normal BMI and did not smoke. A possible explanation for these findings could be the use of oral hormonal contraceptives. Similarly, in a recent study [6], total cholesterol levels were significantly higher in contraceptive users compared to nonusers with similar BMI. Throughout adolescence, total cholesterol levels as well as HDL-C and LDL-C tend to decrease, while in the last years of puberty, girls may have a slight increase of HDL-C level [11]. Thus, in this study, it is possible that oral hormonal contraceptive use was the cause of persistent elevation in total cholesterol levels in the five young women referred to previously because they were neither obese nor smokers. One of the main changes observed in the lipid profile of adolescents is the decline in HDL-C starting around 10 years of age, followed by a slight increase in girls around their 14th birthday, probably due to the effect of estrogen on lipoproteins [12]. Users of low-dose oral hormonal contraceptive, especially those containing the new progestogens, such as desogestrel or gestodene, show an increase in serum levels of HDL-C [6,13]. Similar to the findings described in the literature, the results of the present study seem to indicate that the use of oral hormonal contraceptives may be associated with elevation of HDL-C levels. The role of triglycerides in atherosclerosis is not quite clear but some studies have suggested that their increase may lead to elevation of coagulation factors (VII, VIII and X) and changes in fibrinolytic activity [14]. In most children, hypertriglyceridemia is a manifestation of VLDL-C increase with a generally normal cholesterol level. The use of estrogen, glycocorticoids, diuretics, alcohol or the presence of diabetes, chronic renal failure and hypothyroidism are the most common causes of secondary hypertriglyceridemia and is explained by the reduction in lipoprotein lipase activity in removing excess serum triglycerides [15]. Some studies have reported an increase in serum levels of triglycerides in users of oral hormone contraceptives, regardless of their composition [12]. This finding could reflect an increase in the hepatic synthesis of VLDL-C or a decrease of serum VLDL-C lipolysis by lipoprotein lipase.
It could also be attributed to estrogen action in changing liver lipase activity. In this study, triglyceride levels increased significantly after starting contraceptives, but did not exceed normal range (130 mg/dL). There are few published studies similar to this one where adolescents using OC were prospectively followed over a long period of time (3 years). This may be due, in part, to difficulties in the follow-up and clinical control of this population [16]. Most studies compare differences between users and nonusers of OC using data collected through questionnaires and a single exam [17,18]. In modern times, sexual initiation starts early and pregnancy is frequently delayed until the thirties. This has created a demand for contraceptive methods that are at the same time efficient and safe to use for a long period of time. Our findings suggest the prolonged use of OC may induce the beginning of atherogenesis. This raises an important question: should adolescent users of OC be submitted to routine periodic lipid profile screening? While there is no consensus in the scientific literature, most recommend these tests only for women with coronary disease or other risk factors [4]. Nevertheless, oral hormonal contraceptives tend to be used by increasingly younger women and the early detection of lipid alterations could be important, leading to preventive measures such as modification of eating habits, initiation of physical activity and periodic physical exams. All these steps are important in reducing long-term morbidity, even for young people. The clinical relevance of our findings can only be evaluated through large studies with adolescents using COC over a long period of time.
References [1] WHO. Cardiovascular disease and steroid hormone contraception. Technical Report Series, 877. Geneva: WHO; 1998. p. 89. [2] Farley TMM, Collins J, Schlesselman JJ. Hormonal contraception and risk of cardiovascular disease. Contraception 1998;57:211 – 30. [3] WHO. Improving access to quality care in family planning: medical eligibility criteria for initiating and continuing use of contraceptive methods. Geneva7 World Health Organization; 1996. p. 143. [4] National Cholesterol Education Program (NCEP). Highlights of the report of the Expert Panel on blood cholesterol levels in children and adolescents. Pediatrics 1992;89:495 – 500. [5] Pollack AE. Teen contraception in the 1990. J Sch Health 1992;62: 288 – 93. [6] Paulus D, Saint-Remy A, Jeanjean M. Oral contraception and cardiovascular risk factors during adolescence. Contraception 2000;62: 113 – 6. [7] O’Neil CE, Nickas TA, Myers L, Johnson CC, Berenson G. Cardiovascular risk factors and behavior lifestyles of young women: implications from findings of the Bogalusa Heart Study. Am J Med Sci 1997;314:385 – 95. [8] Croft JB, Freedman DS, Cresanta JL, et al. Adverse influences of alcohol, tobacco, and oral contraceptive use on cardiovascular risk factors during transition to adulthood. Am J Epidemiol 1987;126: 202 – 13.
C.A.F. Guazzelli et al. / Contraception 71 (2005) 118–121 [9] Williams CI, Campanaro LA, Squillace M, Bollella M. Management of childhood obesity in pediatric practice. Ann N Y Acad Sci 1997; 817:225 – 32. [10] Freedman DS, Burke GL, Harsha DW, et al. Relationship of changes in obesity to serum lipid and lipoprotein changes in a childhood and adolescence. Am Med Assoc 1985;254:515 – 20. [11] Berenson GS, Srinivasan SR, Bao W. Precursors of cardiovascular risk in young adults from a biracial (black–white) population: the Bogalusa Heart Study. Ann N Y Acad Sci 1997;817:189 – 98. [12] O’Brien T, Nguyen TT. Lipids and lipoproteins in women. Mayo Clin Proc 1997;72:235 – 44. [13] Speroff L, Decherney A. The advisory board for the new progestins. Evaluation of a new generation of oral contraceptives. Obstet Gynecol 1993;81:1034 – 47.
121
[14] National Institutes of Health. Consensus development panel on triglycerides, high-density lipoprotein, and coronary heart disease. J Am Med Assoc 1993;269:505 – 10. [15] Chait A, Brunzell JD. Severe hypertriglyceridemia: role of familial and acquired disorders. Metabolism 1983;32:209 – 13. [16] Davis AJ. The role of hormonal contraception in adolescents. Am J Obstet Gynecol 1994;170:1581 – 5. [17] Lioyd T, Lin HM, Matthews AE, Bentley CM, Legro RS. Oral contraceptive use by teenage women does not affect body composition. Obstet Gynecol 2002;100:235 – 9. [18] Nawrot TS, Hond ED, Fagard RH, Hoppenbrouwers K, Staessen JA. Blood pressure, serum total cholesterol and contraceptive pill in 17year-old girls. J Cardiovasc Risk 2003;10:438 – 42.
Original research article
Evaluation of lipid profile in adolescents during long-term use of combined oral hormonal contraceptives Christina Aparecida Falbo Guazzellia,*, Prescilla Chow Lindseya, Fabio Fernando de Arau´joa, Ma´rcia Barbieria, Carlos Alberto Pettab, Jose Mendes Aldrighic a
Family Planning Clinic, Department of Obstetrics and Gynecology, Universidade Federal de Sa˜o Paulo (UNIFESP), Sa˜o Paulo CEP 09090050, Brazil b Human Reproduction Unit, Department of Obstetrics and Gynecology, School of Medicine, Universidade Estadual de Campinas (UNICAMP), 13083530 Campinas, Brazil c Department of Maternal Health, School of Public Health, University of Sa˜o Paulo, Sa˜o Paulo 05663030, Brazil Received 24 October 2003; revised 29 July 2004; accepted 2 August 2004
Abstract The study evaluated the effects of the long-term use of a combined oral hormonal contraceptive containing 30 Ag ethinyl estradiol and 75 Ag gestodene in adolescents. Thirty-three volunteers, aged from 14 to 19 years, who used the oral contraceptive for three consecutive years, were studied. Evaluation of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides was made before use and after 1, 2 and 3 years. During the 3-year study period, total cholesterol, HDL-C, LDL-C and triglyceride levels were significantly higher than previous measurements, but average values did not exceed the normal range. Compared to the first year, the second- and third-year cholesterol, HDL-C, LDL-C and triglyceride levels were not significantly different. D 2005 Elsevier Inc. All rights reserved. Keywords: Adolescents; Contraceptives; Hormonal contraceptives; Cholesterol; Triglycerides
1. Introduction
2. Materials and methods
Combined oral contraceptives (COC) are popular among adolescents since they are highly efficient and easy to use. Although the consequences of their use have been extensively reviewed in adult women, there have been few studies involving adolescents. The most feared complications of oral hormonal contraceptives include thromboembolic phenomena and cardiovascular disease [1]. Previous studies have demonstrated that atherosclerosis is a process that begins in young adults and can be accelerated by the presence of risk factors such as smoking, alcohol, obesity and oral hormonal contraceptives [2]. The objective of this study was to evaluate the effects of the long-term use of monophasic combined hormonal oral contraceptives on the lipid metabolism of adolescents.
All adolescents attending the Family Planning Clinic of Sa˜o Paulo Federal University who elected COC as their method of choice were invited to participate in the study. Of the initial 80 participants, 58 completed 1 year of study, 50 completed 2 years and 33 completed 3 years. Therefore, the study population consisted of 33 adolescents who used monophasic oral hormone contraceptive (21 tablets monthly containing gestodene 75 Ag and ethinyl estradiol 30 Ag each) who were prospectively evaluated for 3 years. The study was approved by the Ethics Committee of UNIFESP (Universidade Federal de Sa˜o Paulo) and all participants signed an informed consent form. The exclusion criteria were: WHO medical eligibility criteria categories 3 and 4 [3]; use of an oral hormonal contraceptive in the three previous months prior to entry in the study; concomitant use of medications that might interfere in lipid metabolism (thiazides, corticosteroids, hblockers, cyclosporine); smoking; cholesterol values higher than 199 mg/dL at baseline [4]; hemoglobin lower than 12 g/dL; body mass index (BMI; weight/height2) higher than
* Corresponding author. Tel.: +55 11 557 22605; fax: +55 11 557 22605. E-mail address: [email protected] (C.A.F. Guazzelli). 0010-7824/$ – see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.contraception.2004.08.002
C.A.F. Guazzelli et al. / Contraception 71 (2005) 118–121
119
95th percentile; family history of thromboembolic diseases or myocardial infarct before 50 years of age in men and 60 years in women. All participants were healthy and had normal physical and gynecological exams before starting contraceptive use. These were repeated every 3 months during the 3-year study period. The lipid profile consisted of total cholesterol, highdensity lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides before (T0) and after 1 (T1), 2 (T2) and 3 (T3) years of oral hormonal contraceptive use. The levels of each parameter obtained at baseline were considered as control values for each patient. Total cholesterol values below 199 mg/dL and LDL-C below 129 mg/dL were considered normal and triglyceride levels were classified as adequate when lower than 131 mg/dL [4]. Measurements were made throughout the 3 years of the study, immediately after each sample collection.
Compared to baseline values, total cholesterol levels increased significantly after 1 (T1), 2 (T2) and 3 (T3) years of contraceptive use (Table 1), as did HDL-C values. At baseline, 11 adolescents had HDL-C below 35 mg/dL. After starting contraceptives and throughout the study period, only four measurements were lower than 35 mg/dL. In five adolescents, total cholesterol level rose above normal limits (199 mg/dL) during the 3-year study period. None of these patients had BMI above the 95th percentile. Triglycerides and LDL-C also increased significantly after 1, 2 and 3 years of oral hormonal contraceptive use (Table 1). In the second and third years of the study, cholesterol, HDL-C, LDL-C and triglyceride levels did not differ significantly from those obtained in the first year.
2.1. Laboratory assays
4. Discussion
Enzyme kits and an auto-analyzer were used to determine total cholesterol, HDL-C and triglyceride levels. Cholesterol was measured on supernatant using the ADVIA 1650-Bayer colorimetric enzyme kit. According to solution characteristics, concentrations up to 500 mg/dL were detectable. HDL-C was quantified using the same technique as for cholesterol, after precipitation with dextran sulfate. VLDLC was obtained dividing triglyceride values by 5. This method could be used since triglycerides levels were b 400 mg/dL in all samples.
Atherosclerosis is an important cause of adult mortality and its prevention can be initiated in childhood through adequate evaluation of family history (hypercholesterolemia or early myocardial infarct) and periodic exams of cholesterol levels. Several additional risk factors have been identified, such as smoking, obesity, hypertension, diabetes and high levels of cholesterol [1]. Adolescence is a time of great personal changes and frequently marks the beginning of undesirable habits such as smoking, sedentary lifestyle and improper eating patterns, such as the ingestion of large amounts of food rich in saturated fat. Frequently, it is also the period of sexual initiation, hence the need for contraceptive methods. Adolescents frequently prefer oral hormonal contraceptives because they are highly efficient, reduce dysmenorrhea and improve menstrual cycle control [5]. Consequences of oral contraceptive use have been widely studied in adult women but the adolescent population has been less studied. Therefore, recommendations for the prescription of OC to adolescents are largely based on guidelines originally designed for adult women [6]. In this study, we observed a statistically significant elevation in total cholesterol, HDL-C, LDL-C and triglycerides levels. Although this increase alone may not jeopardize the health of a young adult, it could increase the effect of other risk factors [6].
2.2. Statistical analysis The sample size was calculated as a minimum of 30 patients followed-up for 3 years, with a 90% power to detect differences of 1 standard deviation comparing the four annual averages. Significance was established at 5%. A paired t test was used to compare average values of each variable (total cholesterol, HDL-C, LDL-C and triglycerides). Confidence intervals were set at 95% (c =0.95 or 95%). 3. Results The mean age at entry was 16.6 years and average age at menarche was 12.4 years with a standard error of 0.2 years. The mean age at first intercourse was 15.4 and 72.7% of the patients had no previous pregnancies.
Table 1 Lipid profile of 33 adolescents using oral hormonal contraceptives for 3 years Parameter
Baseline (T0)
After 1 year (T1)
After 2 years (T2)
After 3 years (T3)
Cholesterol HDL-C LDL-C Triglycerides
148.06F23.78 40.24F10.07 91.7F19.15 80.52F32.34
178.82F36.36* 47.97F10.51* 111.21F30.08* 98.30F40.54**
184.06F35.05* 50.85F10.6* 113.55F32.35* 98.33F43.61**
184.15F36.35* 53.94F14.59* 111.39F37.51** 99.45F44.74**
* p b .001 paired t test in comparison with baseline values. ** p b .05.
120
C.A.F. Guazzelli et al. / Contraception 71 (2005) 118–121
In adolescence, interaction of risk factors is common, especially smoking and obesity. Since up to 30 –35% of adolescents smoke and this habit could modify their lipid profile, we decided to exclude all smokers from this study [7,8]. Obesity, a frequent condition in adolescents, has been associated with elevated levels of triglycerides and total cholesterol and a decrease in HDL-C [9]. These lipoprotein modifications may predispose to lipid deposits in the aorta and coronaries, initiating atherosclerosis [10]. It should be noted that five young women who showed persistent and abnormal increase in cholesterol levels throughout the 3-year study period presented normal BMI and did not smoke. A possible explanation for these findings could be the use of oral hormonal contraceptives. Similarly, in a recent study [6], total cholesterol levels were significantly higher in contraceptive users compared to nonusers with similar BMI. Throughout adolescence, total cholesterol levels as well as HDL-C and LDL-C tend to decrease, while in the last years of puberty, girls may have a slight increase of HDL-C level [11]. Thus, in this study, it is possible that oral hormonal contraceptive use was the cause of persistent elevation in total cholesterol levels in the five young women referred to previously because they were neither obese nor smokers. One of the main changes observed in the lipid profile of adolescents is the decline in HDL-C starting around 10 years of age, followed by a slight increase in girls around their 14th birthday, probably due to the effect of estrogen on lipoproteins [12]. Users of low-dose oral hormonal contraceptive, especially those containing the new progestogens, such as desogestrel or gestodene, show an increase in serum levels of HDL-C [6,13]. Similar to the findings described in the literature, the results of the present study seem to indicate that the use of oral hormonal contraceptives may be associated with elevation of HDL-C levels. The role of triglycerides in atherosclerosis is not quite clear but some studies have suggested that their increase may lead to elevation of coagulation factors (VII, VIII and X) and changes in fibrinolytic activity [14]. In most children, hypertriglyceridemia is a manifestation of VLDL-C increase with a generally normal cholesterol level. The use of estrogen, glycocorticoids, diuretics, alcohol or the presence of diabetes, chronic renal failure and hypothyroidism are the most common causes of secondary hypertriglyceridemia and is explained by the reduction in lipoprotein lipase activity in removing excess serum triglycerides [15]. Some studies have reported an increase in serum levels of triglycerides in users of oral hormone contraceptives, regardless of their composition [12]. This finding could reflect an increase in the hepatic synthesis of VLDL-C or a decrease of serum VLDL-C lipolysis by lipoprotein lipase.
It could also be attributed to estrogen action in changing liver lipase activity. In this study, triglyceride levels increased significantly after starting contraceptives, but did not exceed normal range (130 mg/dL). There are few published studies similar to this one where adolescents using OC were prospectively followed over a long period of time (3 years). This may be due, in part, to difficulties in the follow-up and clinical control of this population [16]. Most studies compare differences between users and nonusers of OC using data collected through questionnaires and a single exam [17,18]. In modern times, sexual initiation starts early and pregnancy is frequently delayed until the thirties. This has created a demand for contraceptive methods that are at the same time efficient and safe to use for a long period of time. Our findings suggest the prolonged use of OC may induce the beginning of atherogenesis. This raises an important question: should adolescent users of OC be submitted to routine periodic lipid profile screening? While there is no consensus in the scientific literature, most recommend these tests only for women with coronary disease or other risk factors [4]. Nevertheless, oral hormonal contraceptives tend to be used by increasingly younger women and the early detection of lipid alterations could be important, leading to preventive measures such as modification of eating habits, initiation of physical activity and periodic physical exams. All these steps are important in reducing long-term morbidity, even for young people. The clinical relevance of our findings can only be evaluated through large studies with adolescents using COC over a long period of time.
References [1] WHO. Cardiovascular disease and steroid hormone contraception. Technical Report Series, 877. Geneva: WHO; 1998. p. 89. [2] Farley TMM, Collins J, Schlesselman JJ. Hormonal contraception and risk of cardiovascular disease. Contraception 1998;57:211 – 30. [3] WHO. Improving access to quality care in family planning: medical eligibility criteria for initiating and continuing use of contraceptive methods. Geneva7 World Health Organization; 1996. p. 143. [4] National Cholesterol Education Program (NCEP). Highlights of the report of the Expert Panel on blood cholesterol levels in children and adolescents. Pediatrics 1992;89:495 – 500. [5] Pollack AE. Teen contraception in the 1990. J Sch Health 1992;62: 288 – 93. [6] Paulus D, Saint-Remy A, Jeanjean M. Oral contraception and cardiovascular risk factors during adolescence. Contraception 2000;62: 113 – 6. [7] O’Neil CE, Nickas TA, Myers L, Johnson CC, Berenson G. Cardiovascular risk factors and behavior lifestyles of young women: implications from findings of the Bogalusa Heart Study. Am J Med Sci 1997;314:385 – 95. [8] Croft JB, Freedman DS, Cresanta JL, et al. Adverse influences of alcohol, tobacco, and oral contraceptive use on cardiovascular risk factors during transition to adulthood. Am J Epidemiol 1987;126: 202 – 13.
C.A.F. Guazzelli et al. / Contraception 71 (2005) 118–121 [9] Williams CI, Campanaro LA, Squillace M, Bollella M. Management of childhood obesity in pediatric practice. Ann N Y Acad Sci 1997; 817:225 – 32. [10] Freedman DS, Burke GL, Harsha DW, et al. Relationship of changes in obesity to serum lipid and lipoprotein changes in a childhood and adolescence. Am Med Assoc 1985;254:515 – 20. [11] Berenson GS, Srinivasan SR, Bao W. Precursors of cardiovascular risk in young adults from a biracial (black–white) population: the Bogalusa Heart Study. Ann N Y Acad Sci 1997;817:189 – 98. [12] O’Brien T, Nguyen TT. Lipids and lipoproteins in women. Mayo Clin Proc 1997;72:235 – 44. [13] Speroff L, Decherney A. The advisory board for the new progestins. Evaluation of a new generation of oral contraceptives. Obstet Gynecol 1993;81:1034 – 47.
121
[14] National Institutes of Health. Consensus development panel on triglycerides, high-density lipoprotein, and coronary heart disease. J Am Med Assoc 1993;269:505 – 10. [15] Chait A, Brunzell JD. Severe hypertriglyceridemia: role of familial and acquired disorders. Metabolism 1983;32:209 – 13. [16] Davis AJ. The role of hormonal contraception in adolescents. Am J Obstet Gynecol 1994;170:1581 – 5. [17] Lioyd T, Lin HM, Matthews AE, Bentley CM, Legro RS. Oral contraceptive use by teenage women does not affect body composition. Obstet Gynecol 2002;100:235 – 9. [18] Nawrot TS, Hond ED, Fagard RH, Hoppenbrouwers K, Staessen JA. Blood pressure, serum total cholesterol and contraceptive pill in 17year-old girls. J Cardiovasc Risk 2003;10:438 – 42.