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 Table of Contents  
Year : 2016  |  Volume : 33  |  Issue : 3  |  Page : 257-262

Effect of Implanon (etonogestrel) implant on serum lipids and lipoproteins

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 Publication8-Feb-2017

Correspondence Address:
A O Aisien
Department of Obstetrics and Gynaecology, University of Benin Teaching Hospital, Benin City, Edo State
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0189-5117.199812

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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

How to cite this URL:
Aisien A O, Idogun S E. Effect of Implanon (etonogestrel) implant on serum lipids and lipoproteins. Trop J Obstet Gynaecol [serial online] 2016 [cited 2023 Jun 1];33:257-62. Available from: https://www.tjogonline.com/text.asp?2016/33/3/257/199812

  Introduction Top

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 Top

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.


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 Top

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 Top

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 Top

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


Conflicts of interest

There are no conflicts of interest.

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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.  Back to cited text no. 60


  [Figure 1]

  [Table 1], [Table 2]


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