|
 
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| ORIGINAL ARTICLE |
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| Year : 2016 | Volume
: 33
| Issue : 3 | Page : 257-262 |
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Effect of Implanon (etonogestrel) implant on serum lipids and lipoproteins
AO Aisien1, SE Idogun2
1 Department of Obstetrics and Gynaecology, University of Benin Teaching Hospital, Benin City, Edo State, Nigeria
2 Department of Chemical Pathology, University of Benin Teaching Hospital, Benin City, Edo State, Nigeria
| Date of Web Publication | 8-Feb-2017 |
Correspondence Address:
A O Aisien
Department of Obstetrics and Gynaecology, University of Benin Teaching Hospital, Benin City, Edo State
Nigeria
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0189-5117.199812
Background: Since derangements of lipids and lipoproteins are associated with steroidal contraceptives and could be a consequent of cardiovascular diseases, it is important to study the association with Implanon implant.
Objective: Evaluation of serum lipids and lipoproteins of Implanon users after 24 months of use.
Materials and Methods: The longitudinal study of 46 women who had Implanon inserted was evaluated at preinsertion, 6, 12, and 24 months for serum lipids and lipoproteins.
Results: The mean age and parity of the users were 34.3 ± 4.9 years and 3.0 ± 2.0. The mean weight and blood pressure were 72.2 ± 11.9 kg and 118.3 ± 13.2/76.8 ± 8.6 mmHg. The serum cholesterol and triglycerides were 136.5 ± 16.9 mg/dl and 49.6 ± 14.7 mg/dl at preinsertion. At 6 months, the serum cholesterol rose without significant changes at 6 months, i.e., 138.6 ± 5.4 mg/dl (P = 0.06) and at 12 months, i.e. 137.9 ± 14.3 mg/dl (P = 0.44) of the study. The mean value showed an insignificant reduction at 24 months, i.e., 133.9 ± 12.5 mg/dl (P = 0.24). The serum triglycerides did not change significantly at 6 months -50.8 ± 11.9 (P = 0.42), 12 months -48.9 ± 9.2 (P = 0.66), and 24 months of the study -48.8 ± 10.1 mg/dl (P = 0.73) when compared with the preinsertion mean value. The high-density lipoprotein cholesterol was 52.9 ± 6.3 mg/dl at preinsertion. The serum value reduced significantly at 12 months of the study to 51.1 ± 5.9 mg/dl (P = 0.03) without any significant changes at 6 months, i.e., 51.4 ± 7.4 mg/dl (P = 0.09), and at 24 months of the study, i.e., 51.4 ± 7.9 mg/dl (P = 0.38). The low-density lipoprotein cholesterol was 73.3 ± 14.9 mg/dl at insertion. The mean value significantly increased at 6 months, i.e., 77.2 ± 13.2 mg/dl (P = 0.01), 12 months, i.e., 77.2 ± 13.2 mg/dl (P = 0.05) of study with an insignificant reduction at 24 months, i.e., 72.7 ± 12.7 mg/dl (P = 0.79).
Conclusion: The observed changes in the serum lipids and lipoproteins which are expected to dissipate with time were within normal values. Keywords: Implanon; lipid; profile.
How to cite this article:
Aisien A O, Idogun S E. Effect of Implanon (etonogestrel) implant on serum lipids and lipoproteins. Trop J Obstet Gynaecol 2016;33:257-62 |
| Introduction | |  |
Hormonal method of contraception has been in use since 1960 as combined oral contraceptive pill.[1] Decades later, other hormonal methods were developed to meet the criteria of an ideal family planning method such as being safe, free from side effects, convenient to use, not provider dependent, long lasting, unrelated to coitus, easily available, accessible, and affordable. This led to the development of a six-capsule (Norplant R) long-acting reversible contraceptive (LARC) method by the population council in 1966.[2] Norplant R is a progestogen (levonorgestrel) only method of contraceptive, introduced into Nigeria in 1985. They were found suitable by women of all ages, who did not want to become pregnant for several years, women who wanted no more children but did not want or could not obtain sterilization, and women who wanted effectiveness of a hormonal method without the side effects of estrogen.[3],[4],[5],[6] Implanon (etonogestrel) is a second generation implant developed by Organon because of need to reduce some of the problems associated with the six implant system. Even though it had been in use for some time,[7],[8] it was only introduced into Nigeria in 2006.
It is known that despite several modifications in the formulation of steroidal contraceptives, they are not free from side effects. They cause changes in the induction of protein synthesis, carbohydrate, lipid metabolism, and influences on factors of coagulation as well as menstrual abnormalities.[5], 6, [9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19]
Studies established a significant increase risk of atherosclerotic vascular disease and ischemic vascular disease in women who used combined oral contraceptive pills with more than 50 µg of estrogen.[20],[21],[22],[23],[24],[25] This led to the manufacture of 30–35 µg of estrogen ethinyl estradiol in the combined oral contraceptive pills. Some other studies [26],[27],[28],[29] had also found higher relative risk of venous thromboembolism among current users of low-dose estrogen combined oral contraceptives containing third-generation progestins such as desogestrel or gestodene.
Findings on postmenopausal women who used estrogen replacement therapy had, however, demonstrated the protective effects of estrogen in reducing the risk of atherosclerosis and ischemic heart disease.[30],[31] Estrogen increased the concentration of high-density lipoprotein cholesterol (HDLC).[32],[33],[34] Reports had shown that progestogen lowers the HDLC, and hence predisposition to coronary heart disease.[35],[36],[37] The mechanism of action of levonorgestrel may be due to its androgenic and antiestrogenic properties.[35],[36] The effect causes increase in hepatic and endothelial lipase with a breakdown of high-density lipoprotein in the liver.
Etonogestrel is an active metabolite of the synthetic progestin desogestrel.[15] It is a third-generation progestogen, a structural analog of 19-nortestoterone, which is used in combined oral contraceptive pill. Implanon is single rod nonbiodegradable implant which contains 68 mg of etonogestrel. One rod is inserted subdermally in the inner side of the client's upper arm approximately 6–8 cm or three to four fingers breath above the elbow once in 3 years. The etonogestrel is absorbed into the circulation and becomes 100% bioavailable.[15] The rate of release in the first 6 weeks is 60–70 mcg/day. It decreases to a release rate of 35–45 mcg/day at the end of the 1st year. The release rate decreases to 30–40 mcg/day in the 2nd year and by the end of the 3rd year, the release rate has fallen to about 25–30 mcg/day.
The reports in the literature on lipids and lipoproteins in Implanon users had shown inconsistencies. Some studies showed a reduction in the HDLC.[38],[39] While no change was reported in another study.[40] Inal et al.[40] in their 3-year study reported statistically significant increases in cholesterol and triglycerides concentrations that were within normal ranges among the seventy users. Some other studies [39],[41] reported decrease values. The low-density lipoprotein cholesterol (LDLC) showed no change in the 3-year study of Inal et al.[40] Suherman et al.[41] however, reported a reduction in value. In all these studies, there was no compromise in the health of the patients.
Implanon has gained a considerable popularity among its users since the introduction as an addition to the client's method mix. Health risk is usually one of the reasons given for unmet need in family planning. This factor can contribute to a reduction in contraceptive prevalence and expose women with high-risk pregnancies to maternal mortality and morbidity. Studies that will continue to demonstrate the safety of family planning methods are, therefore, important for counseling and elimination of undue fear among acceptors, hence, the reason for this study.
| Materials and Methods | | |
One hundred and ninety clients accepted family planning methods between February and March 2007, out of which fifty chose Implanon. Forty-six out of the fifty healthy, sexually active informed volunteers aged between 24 and 45 years were enrolled for the study. They were not breastfeeding. Had not received injectable contraceptives 6 months preceding the study. All requesting clients with a history of hypertension, cardiac, renal diseases, diabetes mellitus, and those on lipid-lowering drugs were excluded from the study. The users were having their normal regular menstrual cycle at the time of recruitment into the study.
Clients fasted overnight before family planning clinic attendance. Five milliliters of blood was collected and dispensed into plain bottles without anticoagulant for the determination of cholesterol, triglycerides, and HDLC. The samples were left to clot and the serum separated by centrifugation (3000 r.p.m for 10 min) and subsequently frozen at a temperature of −20°C until assayed in batches. The blood samples were collected between 8 h and 10 h at the time of insertion, and at 6, 12, and 24 months postinsertion. Each client was her own control. The lipids were analyzed by established methods. Total cholesterol assay was by modified Liebermann–Burchard's method of Abel et al.[42] Triglyceride was assayed using enzymatic method of Bucolo and David 1973.[43] HDLC was by precipitation method of Lopes-Virella et al., 1977.[44] LDLC was calculated by indirect method using Friedewald et al., 1972,[45] equation as follows:
LDL = C – HDLC − T/5 mg/dl
All assay procedures were carried out in duplicate, and the intra- and inter-assay coefficient of variation was maintained at 5% and 7%, respectively.
The study was approved by the Ethical Committee of the institution while the clients signed informed consents before their participation in the study.
Weight measurement
Each client was weighed using a standard scale with fine adjustment. Apart from the normal clothing on the client's body, other accessories such as bangles, shoes, and head wears were removed before weighing. The weight of each client was recorded in kilogram (kg) at insertion, 6, 12, and 24 months postinsertion of the Implanon.
Blood pressure measurement
The client's blood pressure in millimeter of mercury (mmHg) was measured in a sitting position, using the standard mercury sphygmomanometer. The cuff was applied to the upper two-thirds of the right arm and was inflated until the brachial artery pulsation disappeared. The cuff pressure was slowly released while the diaphragm of the Littman's stethoscope was applied over the brachial artery. The appearance of the Korotkoff sounds was taken as the systolic blood pressure, whereas the disappearance of the same sound was used as the diastolic blood pressure in all the participants. The recording was done at the time of insertion, 6, 12, and 24 months following insertion.
Analysis
The forty users who had complete records at 24 months were analyzed. Paired t-test was used for statistical analysis. The level of significance was set at P < 0.05. The remaining users dropped out of the study because they were inconsistent.
| Results | | |
Sociodemographic characteristics
The age range and mean ± standard deviation (SD) of the users were 24–45 years and 34.3 ± 4.9, respectively. The parity ranged between 0 and 6 with a mean ± SD of 3 ± 2.
Physical characteristics
Body weight (kg)
The mean body weight of the users at insertion was 72.2 ± 11.9 kg. There was a slight reduction in the body weight at 6 months, i.e., 71.0 ± 10.6 kg (P = 0.14), followed by an insignificant increases in body weight at 12 and 24 months of the study, i.e., 72 ± 11.4 kg (P = 0.78) and 72.3 ± 11.5 kg (P = 0.87) [Table 1]. | Table 1: Mean± standard deviation of the weight and blood pressure at preinsertion, 6, 12, and 24 months
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Blood pressure
The mean value of the blood pressure of the users at the time of insertion was systolic of 118.3 ± 13.2 mmHg and diastolic of 76.8 ± 8.6 mm Hg. These values showed a significant decrease at 12 months with systolic of 110.3 ± 11.7 mmHg (P = 0.001) and diastolic of 73.5 ± 8.6 mmHg (P = 0.07). There were no statistically significant changes in the values at 6 months and at 24 months with a systolic of 119.8 ± 13.5 mmHg (P = 0.47) and diastolic of 75.8 ± 7.8 mmHg (P = 0.37) at 6 months and a systolic of 116 ± 8.7 mmHg (P = 0.32) and diastolic of 76 ± 7.8 mmHg (P = 0.63) at 24 months of the study [Table 1].
Total serum cholesterol
The total serum cholesterol of the users showed a mean ± SD of 136.5 ± 16.9 mg/dl at insertion. At 6 months and 12 months, the mean values increased slightly without significant changes when compared with the preinsertion mean value, i.e., 138.6 ± 15.4 mg/dl (P = 0.06) and 137.9 ± 14.3 mg/dl (P = 0.44), respectively. At 24 months of the study, the total cholesterol has reduced to a nonsignificant mean value of 133.9 ± 12.5 mg/dl (P = 0.24) [Table 2] and [Figure 1]. | Table 2: Mean± standard deviation of the lipid and lipoprotein at preinsertion 6, 12, and 24 months
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 | Figure 1: Mean values of lipids and lipoproteins over 24-month study period
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Total triglycerides
The preinsertion mean value of the triglycerides was 49.6 mg/dl. The value rose to a nonsignificant mean value of 50.8 ± 11.9 mg/dl (P = 0.42) at 6 months. The mean value subsequently reduced to nonsignificant values at 12 and 24 months follow-up, i.e., 48.9 ± 9.2 mg/dl (P = 0.66) and 48.8 ± 10.1 mg/dl (P = 0.73), respectively [Table 2] and [Figure 1].
High-density lipoprotein cholesterol
The HDLC at preinsertion was 52.9 ± 6.3 mg/dl. The mean value reduced at 6 months to 51.4 ± 7.4 mg/dl (P = 0.09). The reduction in mean value became significant at 12 months of use with a mean value of 51.1 ± 5.9 mg/dl (P = 0.03). The mean reduction continued at 24 months of the study to a nonsignificant mean value of 51.4 ± 7.9 mg/dl (P = 0.38) [Table 2] and [Figure 1].
Low-density lipoprotein cholesterol
The LDLC preinsertion mean value was 73.3 ± 14.9 mg/dl. The value rose significantly to a mean values of 77.2 ± 13.1 mg/dl (P = 0.01) at 6 months and 77.2 ± 13.2 mg/dl (P = 0.05) at 12 months when compared to mean value at insertion. The value gradually reduced to a nonsignificant mean value of 72.7 ± 12.7 mg/dl (P = 0.79) at 24 months [Table 2] and [Figure 1].
| Discussion | | |
The study on lipids profile has shown that mean age of the clients and their parity distribution were comparable to those in the literature.[7],[46],[47],[48],[49],[50],[51] These are women in their reproductive ages who sought for family planning either for birth spacing or limitation of their family because they had completed their family sizes but did not consent to permanent method of contraception. The clients in the study had either reduction in weight, increase or no weight changes over the 24 months of study. The mean value of the clients' weights over the study period, however, did not show any significant change. This observation is important in counseling clients who choose LARC method and show concern about weight changes. Weight changes could take any form. Clients with a tendency to put on weight should be advised on a healthy lifestyle that includes daily exercise and diet management. Some other studies had documented no change in weight [46] or increase in weight.[5],[51],[52],[53],[54] Implanon is a derivative of 19-nortestosterone whose actions are antiestrogenic and androgenic. The observed weight gain in some of the users may have been a consequence of the anabolic effect of the method in addition to normal weight increase over time.[15]
Experiences from studies have shown no changes in blood pressure.[54],[55] The blood pressure changes over the 24 months study period has shown a significant reduction at 12 months similar to those reported in some studies.[19],[46] The trend is advantageous as the women in the study are not predisposed to hypertensive disease.
The effects of Implanon on lipid metabolism are few and inconsistent. Studies [38],[39] that ranged from 6 to 24 months had shown a significant reduction in the value of HDLC. The current study also found reduction in the HDLC that was significant at 12 months of study only. The observed reduction in value was within normal range. The LDLC in the study significantly increases even though within normal value at 6 and 12 months of the study. By 24 months of the study, the value had reduced. Other studies found no change [40] to reduction in the value.[38],[41] Studies on total cholesterol have also shown either a reduction in value [38],[39],[41] or an increase.[40] The current study showed a nonsignificant increase. The triglycerides showed a nonsignificant increase at 6 months of the study only which was also reported in another study.[40] Dilbaz et al.[39] found a reduction of triglycerides in their study.
During the past decade, studies have shown that derangements in lipid and lipoproteins play a major role in the pathogenesis of atherosclerosis and cardiovascular disease.[56],[57],[58],[59],[60] High level of cholesterol may be deposited in plaques on the blood vessel walls leading to narrowing or blocking of the blood vessels. This results in hardening of the arteries (atherosclerosis) and its subsequences of heart disease and stroke. HDLC called “good cholesterol” because it removes excess cholesterol and carries it to the liver for removal. LDLC called “bad cholesterol” because it deposits excess cholesterol in walls of blood vessels which can contribute to atherosclerosis. The within normal changes observed in the lipid and lipoprotein values in this study appeared to reflect the dynamics of lipid and lipoproteins metabolism. It is important to continue to have local contents that document the safety of our women on steroidal contraceptives. This is essential for counseling clients that will ensure continue usage of family method and reduce unmet need and its consequences. The etonogestrel implant probably has an effect on the hepatic endothelial lipase which causes the breakdown of the HDLC in the liver. Such an effect may be transient considering the fact that the release rate of the implant at insertion is about 60 mcg/day and reduced to about 25 mcg/day in the 3rd year.
| Conclusion | | |
Implanon was an acceptable and effective method of contraceptive. The health of the users was not compromised during the study period.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Wharton C, Blackburn R. Lower dose pills. Popul Rep A 1988;7:1-31.  |
| 2. | Segal SJ. The development of NORPLANT implants. Stud Fam Plann 1983;14:159-63. |
| 3. | Facts about an implantable contraceptive: Memorandum from a WHO meeting. Bull World Health Organ 1985;63:485-94. |
| 4. | McCauley AP, Geller JS, Rinehart W, Goldstein SM, Sadler LD, Gottlieb M. Decision for Norplant R programs. Popul Rep 1992;3:1-31. |
| 5. | Aisien AO, Sagay AS, Imade GE, Ujah IA, Nnana OU. Changes in menstrual and haematological indices among Norplant acceptors. Contraception 2000;61:283-6. |
| 6. | Aisien AO, Sagay AS, Imade GE, Ujah IA, Nnana OU. Evaluation of menstrual and haematological parameters, after 36 months of Norplant contraception. J Obstet Gynaecol 2002;22:406-10. |
| 7. | Croxatto HB, Urbancsek J, Massai R, Coelingh Bennink H, van Beek A. A multicentre efficacy and safety study of the single contraceptive implant Implanon. Implanon Study Group. Hum Reprod 1999;14:976-81. |
| 8. | Meirik O, Fraser IS, d'Arcangues C; WHO Consultation on Implantable Contraceptives for Women. Implantable contraceptives for women. Hum Reprod Update 2003;9:49-59. |
| 9. | Sondheimer S. Metabolic effects of the birth control pill. Clin Obstet Gynecol 1981;24:927-41. |
| 10. | Oster P, Arab L, Kohlmeier M, Mordasini R, Schellenberg B, Schlierf G. Effects of estrogens and progestogens on lipid metabolism. Am J Obstet Gynecol 1982;142(6 Pt 2):773-5. |
| 11. | Mammen EF. Oral contraceptives and blood coagulation: A critical review. Am J Obstet Gynecol 1982;142(6 Pt 2):781-90. |
| 12. | Otubu JA, Towobola OA, Aisien AO, Ogunkeye OO. Effects of Norplant contraceptive subdermal implants on serum lipids and lipoproteins. Contraception 1993;47:149-59. |
| 13. | Sagay AS, Imade GE, Aisien AO, Ujah IO, Muazu MA. Glucose metabolism among Norplant users in Northern Nigeria. Contraception 2000;62:19-22. |
| 14. | Aisien AO, Imade GE, Sagay AS, Shobowale MO. Safety, efficacy and acceptability of Norplant R implants in Jos, Northern Nigeria. Trop J Obstet Gynaecol 2004;21:95-9. |
| 15. | Implanon Product Monograph. N.V Organon 2005. p. 1-84. |
| 16. | Aisien AO, Enosolease ME, Shobowale MO. Evaluation of haemostatic function in Nigerian Norplant acceptors after 12 months of use. J Obstet Gynaecol 2005;25:377-81. |
| 17. | Sagay AS, Okeahialam BN, Imade GE, Aisien AO. Evaluation of cardiovascular morbidity in Nigerian women after 3 years of Norplant contraception. Afr J Reprod Health 2008;12:47-53. |
| 18. | Aisien AO, Enosolease ME. Haemostatic function in Norplant (levonorgestrel) users: A 3-year prospective experience in Benin-City, Nigeria. Niger Postgrad Med J 2009;16:126-31.  |
| 19. | Aisien AO, Enosolease ME. Safety, efficacy and acceptability of implanon a single rod implantable contraceptive (etonogestrel) in University of Benin Teaching Hospital. Niger J Clin Pract 2010;13:331-5. [ PUBMED] |
| 20. | Vessey MP, Doll R. Investigation of relation between use of oral contraceptives and thromboembolic disease. Br Med J 1968;2:199-205. |
| 21. | Vessey MP, Doll R. Investigation of relation between use of oral contraceptives and thromboembolic disease. A further report. Br Med J 1969;2:651-7. |
| 22. | Sartwell PE, Masi AT, Arthes FG, Greene GR, Smith HE. Thromboembolism and oral contraceptives: An epidemiologic case-control study. Am J Epidemiol 1969;90:365-80. |
| 23. | Stolley PD, Tonascia JA, Tockman MS, Sartwell PE, Rutledge AH, Jacobs MP. Thrombosis with low-estrogen oral contraceptives. Am J Epidemiol 1975;102:197-208. |
| 24. | Vessey M, Doll R, Peto R, Johnson B, Wiggins P. A long-term follow-up study of women using different methods of contraception – An interim report. J Biosoc Sci 1976;8:373-427. |
| 25. | Roach RE, Helmerhorst FM, Lijfering WM, Stijnen T, Aigra A, Dekkers OM. Combined oral contraceptives: Risk of myocardial infarction and ischaemic stroke. Cochrane Database Syst Rev 2015;CD011054. [Doi: 10.1002/14651858.CD011054.pub2a]. |
| 26. | Spitzer WO, Lewis MA, Heinemann LA, Thorogood M, MacRae KD. Third generation oral contraceptives and risk of venous thromboembolic disorders: An international case-control study. Transnational research group on oral contraceptives and the health of young women. BMJ 1996;312:83-8. |
| 27. | Carr BR, Ory H. Estrogen and progestin components of oral contraceptives: Relationship to vascular disease. Contraception 1997;55:267-72. |
| 28. | Rosenberg L, Palmer JR, Sands MI, Grimes D, Bergman U, Daling J, et al. Modern oral contraceptives and cardiovascular disease. Am J Obstet Gynecol 1997;177:707-15. |
| 29. | Hannaford P. Cardiovascular events associated with different combined oral contraceptives: A review of current data. Drug Saf 2000;22:361-71. |
| 30. | Ross RK, Paganini-Hill A, Mack TM, Arthur M, Henderson BE. Menopausal oestrogen therapy and protection from death from ischaemic heart disease. Lancet 1981;1:858-60. |
| 31. | Grodstein F, Stampfer M. The epidemiology of coronary heart disease and estrogen replacement in postmenopausal women. Prog Cardiovasc Dis 1995;38:199-210. |
| 32. | Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med 1977;62:707-14. |
| 33. | Miller NE, Hammett F, Saltissi S, Rao S, van Zeller H, Coltart J, et al. Relation of angiographically defined coronary artery disease to plasma lipoprotein subfractions and apolipoproteins. Br Med J (Clin Res Ed) 1981;282:1741-4. |
| 34. | Speroff L, Bush T, Castelli WP, Stampfer M. How ERT influences cardiovascular disease. Contemp Ob Gyn 1988;30:108-9. |
| 35. | Bradley DD, Wingerd J, Petitti DB, Krauss RM, Ramcharan S. Serum high-density-lipoprotein cholesterol in women using oral contraceptives, estrogens and progestins. N Engl J Med 1978;299:17-20. |
| 36. | Baggett B, Nash HA. Effects of contraceptive steroids on serum lipoproteins and cardiovascular disease scrutinized at workshop in Bethesda. Contraception 1980;21:115-20. |
| 37. | Meade TW. Effects of progestogens on the cardiovascular system. Am J Obstet Gynecol 1982;142(6 Pt 2):776-80. |
| 38. | Biswas A, Viegas OA, Roy AC. Effect of Implanon and Norplant subdermal contraceptive implants on serum lipids – A randomized comparative study. Contraception 2003;68:189-93. |
| 39. | Dilbaz B, Ozdegirmenci O, Caliskan E, Dilbaz S, Haberal A. Effect of etonogestrel implant on serum lipids, liver function tests and hemoglobin levels. Contraception 2010;81:510-4. |
| 40. | Inal MM, Yildirim Y, Ertopcu K, Avci ME, Ozelmas I, Tinar S. Effect of the subdermal contraceptive etonogestrel implant (Implanon) on biochemical and hormonal parameters (three years follow-up). Eur J Contracept Reprod Health Care 2008;13:238-42. |
| 41. | Suherman SK, Affandi B, Korver T. The effects of Implanon on lipid metabolism in comparison with Norplant. Contraception 1999;60:281-7. |
| 42. | Abel LL, Levy BB, Brodie BB, Kendall FE. A simplified method for the estimation of total cholesterol in serum and demonstration of its specificity. J Biol Chem 1952;195:357-66. |
| 43. | Bucolo G, David H. Quantitative determination of serum triglycerides by the use of enzymes. Clin Chem 1973;19:476-82. |
| 44. | Lopes-Virella MF, Stone P, Ellis S, Colwell JA. Cholesterol determination in high-density lipoproteins separated by three different methods. Clin Chem 1977;23:882-4. |
| 45. | Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499-502. |
| 46. | Booranabunyat S, Taneepanichskul S. Implanon use in Thai women above the age of 35 years. Contraception 2004;69:489-91. |
| 47. | Agrawal A, Robinson C. An assessment of the first 3 years' use of Implanon in Luton. J Fam Plann Reprod Health Care 2005;31:310-2. |
| 48. | Rai K, Gupta S, Cotter S. Experience with Implanon in a Northeast London family planning clinic. Eur J Contracept Reprod Health Care 2004;9:39-46. |
| 49. | Yildizbas B, Sahin HG, Kolusari A, Zeteroglu S, Kamaci M. Side effects and acceptability of Implanon: A pilot study conducted in Eastern Turkey. Eur J Contracept Reprod Health Care 2007;12:248-52. |
| 50. | Mutihir JT, Nyango DD. One year experience with Implanon sub-dermal implants in Jos, Nigeria. Niger J Clin Pract 2010;13:28-31. |
| 51. | Ojule JD, Oranu EO, Enyindah CE. Experience with Implanon in Southern Nigeria. J Med Med Sci 2012;3:710-4. |
| 52. | Kiriwat O, Patanayindee A, Koetsawang S, Korver T, Bennink HJ. A 4-year pilot study on the efficacy and safety of Implanon, a single-rod hormonal contraceptive implant, in healthy women in Thailand. Eur J Contracept Reprod Health Care 1998;3:85-91. |
| 53. | Reuter S, Smith A. Implanon: User views in the first year across three family planning services in the Trent Region, UK. Eur J Contracept Reprod Health Care 2003;8:27-36. |
| 54. | Funk S, Miller MM, Mishell DR Jr., Archer DF, Poindexter A, Schmidt J, et al. Safety and efficacy of Implanon, a single-rod implantable contraceptive containing etonogestrel. Contraception 2005;71:319-26. |
| 55. | Affandi B, Korver T, Geurts TB, Coelingh Bennink HJ. A pilot efficacy study with a single-rod contraceptive implant (Implanon) in 200 Indonesian women treated for ≤4 years. Contraception 1999;59:167-74. |
| 56. | Gotto AM. Lipid and lipoprotein disorder. In: Pearson TA, Criqui MH, Leupker RV, Oberman A, Wilson M, editors. Primer in Preventive Cardiology. Dallas, TX: American Heart Association; 1994. p. 107-29. |
| 57. | Ginsberg HN. Lipoprotein metabolism and its relationship to atherosclerosis. Med Clin North Am 1994;78:1-20. |
| 58. | Glew RH, Williams M, Conn CA, Cadena SM, Crossey M, Okolo SN, et al. Cardiovascular disease risk factors and diet of Fulani pastoralists of Northern Nigeria. Am J Clin Nutr 2001;74:730-6. |
| 59. | Glew RH, Kassam HA, Bhanji RA, Okorodudu A, VanderJagt DJ. Serum lipid profiles and risk of cardiovascular disease in three different male populations in Northern Nigeria. J Health Popul Nutr 2002;20:166-74. |
| 60. | Chrysohoou C, Panagiotakos DB, Pitsavos C, Kosma K, Barbetseas J, Karagiorga M, et al. Distribution of serum lipids and lipoproteins in patients with beta thalassaemia major; an epidemiological study in young adults from Greece. Lipids Health Dis 2004;3:3. |
[Figure 1]
[Table 1], [Table 2]
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