THE EFFECTS OF SUBDERMAL ETONORGESTREL ON BODY WEIGHT, BLOOD PRESSURE, MENSTRUAL

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THE EFFECTS OF SUBDERMAL ETONORGESTREL ON BODY WEIGHT, BLOOD PRESSURE, MENSTRUAL

AND NON- MENSTRUAL ADVERSE EFFECTS BETWEEN TWO BMI GROUPS

BY

FAIZATUNNOR BT MUHAMAD

A thesis submitted in fulfilment of the requirement for the degree of Master of Obstetrics and Gynaecology

Kulliyyah of Medicine

International Islamic University Malaysia

DECEMBER 2016

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ABSTRACT

The aim of this study is to describe and compare the effects of subdermal etonorgestrel on body weight, body mass index (BMI), blood pressure (BP) - systolic

& diastolic, menstrual, non-menstrual side-effects and to determine overall acceptability of this implant in between two BMI groups: BMI group of ≤23.0 and

>23.0. This is a comparative cross sectional study which was conducted at Lembaga Penduduk dan Pembangunan Keluarga Negara (LPPKN), Kuantan, Pahang from 1st June 2012 until 1st June 2015. All women who had their subdermal etonorgestrel inserted and removed within study period were included. Data on body weight and body mass index, blood pressure, menstrual changes, non-menstrual side effects, and overall acceptability whilst on subdermal etonorgestrel in between two BMI groups (≤23.0 and >23.0) were analyzed. There were 70 women recruited during the study period where 33 of them with BMI of ≤23.0 and 37 were BMI of >23.0. There was no pregnancy reported. The mean difference of weight gain and BMI increment in both group were statistically significant (P<0.001). The changes were more in women with BMI >23.0. There was no change in systolic blood pressure (SBP) in both groups but diastolic blood pressure (DBP) showed the mean increment is statistically significant in BMI >23.0 group. These changes, however, were not significant clinically. Out of 70 women, more than 90% of women experienced menstrual disturbances whilst on subdermal etonorgestrel, being amenorrhea and infrequent bleeding commonly reported. Non-menstrual side effects were reported in 25% of women. Fifteen women had removed the implant prematurely due to menstrual disturbances, non-menstrual side effects and weight gain issues. However, the differences were not statistically significant between two studied groups. The study reported more than 80% of women were satisfied with the use of this method of contraception. In conclusion, subdermal etonogestrel implant is highly effective as a method of contraception in normal, overweight and obese women and its non-contraceptive effects such as on weight gain, menstruation and blood pressure seemed to be comparable.

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APPROVAL PAGE

I certify that I have supervised and read this study and that in my opinion, it conforms to acceptable standards of scholarly presentation and is fully adequate, in scope and quality, as a dissertation for the degree of Master of Obstetrics and Gynaecology.

………..

Mokhtar Awang Supervisor

………..

Dalia F Abdul Wahab Co-Supervisor

………..

Karimah Hanim bt Abdul Aziz Co-Supervisor

I certify that I have read this study and that in my opinion it conforms to acceptable standards of scholarly presentation and is fully adequate, in scope and quality, as a dissertation for the degree of Master of Obstetrics and Gynaecology.

………..

Mohd Shukri Othman External Examiner

This dissertation was submitted to the Department of Obstetrics and Gynaecology and is accepted as a fulfilment of the requirements for the degree of Master of Obstetrics and Gynaecology.

………..

Mokhtar Awang

Head Department of Obstetrics and Gynaecology.

This dissertation was submitted to the Kulliyyah of Medicine and is accepted as a fulfilment of the requirements for the degree of Master of Obstetrics and Gynaecology.

………..

Azmi Md Nor

Dean, Kulliyyah of Medicine

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DECLARATION

I hereby declare that this dissertation is the result of my own investigations, except where otherwise stated. I also declare that it has not been previously or concurrently submitted as a whole for any other degrees at IIUM or other institutions.

Faizatunnor bt Muhamad

Signature ... Date ...

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INTERNATIONAL ISLAMIC UNIVERSITY MALAYSIA DECLARATION OF COPYRIGHT AND AFFIRMATION OF

FAIR USE OF UNPUBLISHED RESEARCH

THE EFFECTS OF SUBDERMAL ETONORGESTREL ON BODY WEIGHT, BLOOD PRESSURE, MENSTRUAL AND NON- MENSTRUAL ADVERSE EFFECTS BETWEEN TWO BMI

GROUPS

I declare that the copyright holders of this dissertation are jointly owned by the student and IIUM.

No part of this unpublished research may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise without prior written permission of the copyright holder except as provided below

1. Any material contained in or derived from this unpublished research may be used by others in their writing with due acknowledgement.

2. IIUM or its library will have the right to make and transmit copies (print or electronic) for institutional and academic purposes.

3. The IIUM library will have the right to make, store in a retrieval system and supply copies of this unpublished research if requested by other universities and research libraries.

By signing this form, I acknowledged that I have read and understand the IIUM Intellectual Property Right and Commercialization policy.

Affirmed by Faizatunnor bt Muhamad

……..……….. ………..

Signature Date

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ACKNOWLEDGEMENTS

Firstly, a special thanks to Prof. Dr. Mokhtar Awang for his continuous support, encouragement and leadership, and for that, I will be forever grateful.

I wish to express my appreciation and thanks to those who provided their time, effort and support for this research especially to my co-supervisor, Assoc. Prof. Dr Dalia F Abdul Wahab, my statistician Asst. Prof Dr Karimah Hanim bt Abd Aziz and all of my colleagues especially Dr Norhayati, Dr Norhasimah, Dr Faizan Irdawaty, Dr Ruztini whom continuously motivate me to finish my research work. To the members of my dissertation committee, thank you for sticking with me.

Finally, it is my utmost pleasure to dedicate this work to my family including my son, for their continuous moral support and also huge understanding with their tender loving care that I will be always forever grateful, and those who granted me the gift of their unwavering belief in my ability to accomplish this goal, thank you all for your support and patience.

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LIST OF TABLES

Table 3.1 The New BMI Classifications for Asians by NICE Guidelines

(BMJ 2014) 8 Table 3.2 Menstrual Bleeding Pattern according to WHO 90- days

Reference Period 9 Table 4.1 Demographic data of the study subjects 11 Table 4.2 Effects of Implanon on body weight between two groups 12

Table 4.3 Effects of Implanon on Body Mass Index (kg/m²) between

two groups 13 Table 4.4 Effects of Implanon on Blood Pressure (SBP) between

two groups 13 Table 4.5 Effects of Implanon on Blood Pressure (DBP) between

two groups 14 Table 4.6 Menstrual Pattern in last 6- month before Implanon removal 15 Table 4.7 Non-Menstrual Side Effects whilst on Implanon between

two BMI groups 15 Table 4.8 Reasons for premature removal of Implanon 16 Table 4.9 Women’s Satisfaction towards Implanon 16

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LIST OF FIGURES

Figure 3.1 Flow chart of research protocol 10

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LIST OF ABBREVIATION

ACOG American Congress of Obstetrician and Gynaecologist BMI Body Mass Index

BP Blood Pressure

CHC Combined Hormonal Contraception DBP Diastolic Blood Pressure

LARC Long Acting Reversible Contraception

LPPKN Lembaga Penduduk dan Pembangunan Keluarga Negara NICE National Institute for Health and Care Excellence

POC Progestin- Only Contraceptives SBP Systolic Blood Pressure

SPSS Statistical Package for the Social Sciences WHO World Health Organization

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CHAPTER ONE INTRODUCTION

1.1 BACKGROUND OF THE STUDY

Implanon is subdermal implant that contains of 68mg etonogestrel (Darney, Patel, Rosen, Shapiro, & Kaunitz, 2009). It is a long acting reversible contraception (LARC) device which highly effective and convenient that can be used by women in most circumstances. It has the highest effectiveness with high level of women’s satisfaction among any other contraceptive method (Fischer, 2008; Jacobstein & Polis, 2014). It is effective within 24 hours of insertion and lasted for 3 years (Darney et al., 2009).

Implanon releases low dose of progestin continuously which inhibits ovulation and thicken the cervical mucus (Croxatto & Mäkäräinen, 1998; Darney et al., 2009) and thinning the endometrial thickness (Fischer, 2008).

The advantages of Implanon are safe, convenience, well accepted, non-oral thus ensure patient’s compliance and quick return to fertility once it is removed (Fischer, 2008). As it is a progestin only contraceptive, it can be used by women who cannot tolerate or not suitable with contraceptive containing oestrogen (Jacobstein &

Polis, 2014) such as in obese patient or those with underlying deep vein thrombosis or heart and liver problem. Unfortunately, it has both menstrual and non-menstrual side effects. It can cause unpredictable bleeding patterns include oligomenorrhoea, amenorrhea, frequent, infrequent or even prolonged bleeding. Other side effects which comprise up to 9% of Implanon user includes acne, weight gain, mood changes, headache, breast tenderness, abdominal pain, allergy and reduce libido (Isley, 2010).

In overweight or obese women, Implanon may have lower efficacy or thought to be less effective compared to normal weight woman as serum concentration of

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progestin are inversely associated to body weight and the dose decreases with time after insertion (Sivin, Nash, & Waldman, 2002). However, the data is limited.

Obese women whom progestogen-only contraceptive (POC) users may have a greater risk in weight gain increment or other adverse health effects related to weight gain such as cardiovascular or endocrine associated problems (Curtis, Ravi, &

Gaffield, 2009). However, Implanon has lower androgenic effect. Thus, compared to other progestins, the side effect of weight gain is less frequently reported. (Balogun, Olaomo, Adeniran, & Fawole, 2014).

In Malaysia, prevalence of obesity among adult females was higher from 7.6%

in 1996 but escalating to 17.4% in 2006 (Wan Mohamud et al., 2011). There is growing concern about safety of contraception in obese and also minimal information regarding the effectiveness and safety of Implanon in relation to body weight. The rationale of this study is to observe the effects of Implanon between two different categories of body mass index, which will help us in the counselling.

1.2 RESEARCH OBJECTIVES

1- To compare the effects of Implanon on body weight, body mass index (BMI), blood pressure (BP) both systolic & diastolic, menstrual, non- menstrual side effects in between two BMI groups.

2- To determine overall acceptability of Implanon user among two BMI groups.

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CHAPTER TWO LITERATURE REVIEW

In this age, incidence of obesity worldwide is escalating (Rodriguez & Edelman, 2011). In Malaysia, from the survey in 2007-2008, the incidence is about 36% and out of these obese adult, 22.5% of them are female with body mass index (BMI) ≥30 (Wan Mohamud et al., 2011). Obesity is known to affect the health of both current and future generations with higher rates of morbidity and mortality in both maternal and fetus (Catalano & Ehrenberg, 2006). It complicates every angle of pregnancy, from conception to birth such as higher rate of intrauterine death, diabetes, fetal anomalies, fetal macrosomia, caesarean delivery and neonatal admission. Children born to obese mothers also are at higher risk for immediate postpartum metabolic problem, future obesity and diabetes themselves. Thus, obesity possesses a significant public health and economic concern (Rodriguez & Edelman, 2011).

Contraception or family planning becomes clinical and public health importance since it can prevent unplanned pregnancy, poor spacing, unfit woman from embarking on pregnancy (Jensen, 2011). Challenges in providing contraception to obese women are concern about potential decreased efficacy and risk of venous thromboembolism compared to normal weight women when taking oestrogen- containing contraceptives (Mornar et al., 2012). American Congress of Obstetricians and Gynaecologist encourage usage of highly effective, long acting progestin only contraceptives, implantable devices in obese women ("ACOG practice bulletin. No.

73: Use of hormonal contraception in women with coexisting medical conditions,"

2006).

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Implanon or subdermal etonogestrel is an established long term reversible contraceptive device. In Europe approximately 10% of women are using long acting reversible contraception (LARC) and out of these, 7% using Implanon (Haimovich, 2009). It is highly effective with low Pearl index or low contraceptive failure which is less than 1%. It is non- oral contraceptive and does not require users continuous action thus increase the user’s compliance (Fischer, 2008). With minimal dose of hormone, hence it is well tolerated and safe (Rodriguez & Edelman, 2011). Since it is progestin only contraceptives, it is suitable for women who have contraindications to oestrogen (Isley, 2010; Teunissen, Grimm, & Roumen, 2014).

Similar to other progestogen-containing contraceptives, an etonogestrel implant usage is associated with an unpredictable bleeding patterns. This includes oligomenorrhoea, amenorrhea, frequent, infrequent and prolonged bleeding (Casey, Long, Marnach, & Bury, 2011; Isley, 2010; Laban, Abd Alhamid, Ibrahim, Elyan, &

Ibrahim, 2012; Mansour, Bahamondes, Critchley, Darney, & Fraser, 2011). Other side effects are acne, weight gain, mood changes, headache, breast tenderness, abdominal pain, allergy and reduced libido and these comprises up to 9% of Implanon users (Isley, 2010).

The effect of obesity on drug pharmacokinetics is poorly understood. The main controversial issue is contraceptive failure that might be attributed by large body surface disproportionate to bioavailability of the drugs. Edelman et al in 2009 reported there were no significance difference in volume of drug distribution between different groups of body mass index ( Edelman, et al., 2009). Implanon has not been studied in women who weight more than 130% of ideal body weight but the study done only involved women over 70kg, however no pregnancies were reported. So, no conclusion

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can be made in relation to the impact of obesity with Implanon’s effectiveness (Graesslin & Korver, 2008).

Weight gain is a major health and personal concern for many women. It is not surprising that women often blame contraception for causation towards their weight gain. This adverse effect is among the commonest reason given for discontinuation of contraception usage. Implanon has not been well studied in regard to weight gain but a few studies showed little or no impact on weight gain (Funk et al., 2005). Similarly, there is minimal robust evidence to suggest that progestogen-only contraception causes significant weight gain compared to non-users (Edelman, 2009; Lopez et al., 1996). On the other hand, in clinical trials of Jadelle use, the average weight change over five years of usage was an increment of 9 pounds and this occur in about 50% of cases (Sivin et al., 2002).

A few studies had been conducted to look into relationships between Implanon and systolic and diastolic blood pressure. Unfortunately the results are equivocal.

Some studies showed decline in blood pressure whereas others revealed increment of blood pressure. Makarainen et al reported with Implanon, both systolic and diastolic blood pressure showed a small mean decrease from baseline at all assessments (Mäkäräinen, van Beek, Tuomivaara, Asplund, & Bennink, 1998). However Urbancsek (1998) revealed clinically significant increased systolic and diastolic blood pressure. While Booranabunyat stated there was no significant changes in diastolic blood pressure but systolic blood pressure declined among Implanon users above 35 years old (Booranabunyat & Taneepanichskul, 2004).

Previous studies documented effects of Implanon in general but this study will try to further categorise the effects of Implanon in obese and non-obese woman and to see any differences between these two groups. This information is crucial during

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contraception counselling especially with those obese women, helping them to understand better hence to ensure the adherence towards Implanon.

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CHAPTER THREE

RESEARCH METHODOLOGY

A cohort study was conducted at Lembaga Penduduk dan Pembangunan Keluarga Negara (LPPKN), Kuantan, Pahang. This study was performed within three years period starting from 1^st June 2012 until 31^st May 2015. The institutional approval was obtained from Director of National Population and Family Development Board of Malaysia.

The inclusion criteria of this study were all agreed women who come to LPPKN had their Implanon inserted and removed within study period. The participants included in the study were sexually active with childbearing potential, free of medical illness and no contraindication to use hormonal contraceptive devices.

Women whom had medical illness such as diabetes mellitus, hypertension, and heart disease, and those whom with irregular menses and were on other hormonal contraception at Implanon insertion were excluded from this study.

The participants were counselled and explained regarding the study, a written consent signed upon agreement to participate with the study. A profoma was used to collect data at the time of Implanon insertion. This was done by the main researcher with the aid of a trained research assistant, to ensure that the contents and meaning were preserved. The profoma comprises of patient’s identification data, demographic data, background obstetric and gynaecological history such as recent contraception used and details on menstrual history. The date of Implanon insertion, blood pressure, body weight and body mass index (BMI) were obtained.

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Women being divided into 2 groups: (BMI ≤23.0 kg/m2), (BMI >23.kg/m²)

based on the new BMI criteria for Asians by National Institute for Health and Care Excellence (NICE) Guidelines (Stegenga, Haines, Jones, & Wilding, 2014) (Table 3.1)

.

Table 3.1 The New BMI Classifications for Asians by NICE Guidelines (BMJ 2014)

BMI(kg/m2) Classification

<18.5 Underweight

18.5-23.0 Normal

23.1-27.5 Overweight

>27.5 Obese

The pre-Implanon insertion data will be kept in LPPKN record office. About one to two follow ups were done to review symptoms or any Implanon- related problems whilst these women on Implanon. Data on weight and their blood pressure were measured and documented upon removal of Implanon and the profoma was completed. Details regarding menstrual patterns six months prior to removal and non- menstrual side effects whilst on Implanon were analysed.

The menstrual patterns were described according to WHO Bleeding Patterns in the 90-day Reference Period. Spotting is defined as bleeding that required less than one pad or tampon per day whereas bleeding is when a woman required more than a pad or tampon per day (Affandi, 1998; Cheng et al., 2000).

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Table 3.2 Menstrual Bleeding Pattern according to WHO 90- days Reference Period Menstrual pattern Definition

Amenorrhoea No bleeding or spotting during 90-day reference period Prolong Bleeding At least one bleeding or spotting episode of >14 days during a

90-day reference period

Frequent Bleeding More than 5 bleeding or spotting episodes during a 90-day reference period

Infrequent Bleeding One or two bleeding or spotting episodes during a 90-day reference period

Normal None of the above

The non- menstrual side effects were analyzed including acne, headache, emotional instability, reduced libido and others. Weight gain was excluded from non- menstrual side effects and was counted as separate entity of adverse side effects. The reasons for premature Implanon removal were also studied. All data will be analyzed using Statistical Package for the Social Sciences (SPSS) Version 20.

Chi square and Fisher Exact Test were used whenever appropriate for categorical data whereas paired T-test was used for numerical data. Level of significance was taken at P value of < 0.05.

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10 Women who attended family

planning clinic from 1^st June 2012- 1^st June 2015 for Implanon insertion. Women who fulfilled exclusion criteria excluded from the study

Exclusion Criteria:

 Having medical illness

 Irregular menses

 On other hormonal contraception prior to Implanon insertion

 Refused to join the study

70 women recruited for the study

Required data documented:

 Weight, BMI

 Blood Pressure

 Menstrual pattern prior to Implanon insertion

BMI ≤ 23.0 BMI > 23.0

Upon Implanon removal, data on:

 Weight, BMI, BP (SBP & DBP)

 Menstrual disturbance

 Non-menstrual disturbance

 Reasons for premature removal

 Women’s satisfaction towards Implanon

 documented, analysed and compared between two BMI groups

Figure 3.1 Flow chart of research protocol

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CHAPTER FOUR RESULTS

4.1 DEMOGRAPHIC VARIABLES

A total of 70 women were enrolled in this study. There were no drop out of study subjects. The demographic data of study subjects are summarized in Table 4.1. The mean age of the study population is 29.11 (4.26) years whereby the youngest was 18 years and the eldest being 39 years. All patients were Malay about 94.3%, except two of the subjects were Chinese. Out of 70 women studied, only 12 (17.1%) were obese (BMI> 27.5) but when we reclassified them into two different groups of BMI, (≤ 23.0- underweight and normal, >23.0- overweight and obese), the percentage of both groups were comparable.

Table 4.1 Demographic data of the study subjects

Variable N % Mean(S.D)

Age 18-39 years 70 100 29.11 (4.26)

Ethnicity Malay 66 94.3

Chinese 2 2.9

Others 2 2.9

Parity Primiparous 22 31.4

Multiparous 47 67.2

Grandmultiparous 1 1.4

BMI ≤ 23.0 33 47.1

>23.0 37 52.9

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4.2 EFFECTS OF IMPLANON ON BODY WEIGHT, AND BMI

All 70 women but 4 out of 33 in BMI ≤ 23.0 and 2 out of 37 in BMI >23.0 had reported weight gain during the study period. The effects of Implanon on body weight was statistically significant in both BMI groups (P<0.001) but the weight increment was more in group of women with BMI >23.0 (Table 4.2). In women with BMI ≤ 23.0, the mean body weight increased from 49.82 to 54.56kg and the mean difference is 4.7 (4.7) whereas in women with BMI >23.0,the mean body weight increased from 66.57 to 74.20kg/m2 and the mean difference is 7.6 (5.3).

Table 4.2 Effects of Implanon on body weight between two groups

Variable Mean SD

Mean Difference

(95% CI)

T P value*

BMI Categories

N Weight at insertion(kg)

Weight at removal(kg)

≤23.0 33 49.82(5.27) 54.56(7.90) 4.7

(6.41, 3.07) 5.80 <0.001

>23.0 37 66.57(7.47) 74.20(10.8) 7.6

(9.38, 5.88) 8.83 <0.001

*Paired t test

Similar to the body weight, the effects of Implanon on BMI was statistically significant in both BMI groups (P<0.001) but the BMI increment was more in group of women with BMI >23.0 (Table 4.3). In women with BMI ≤ 23.0, the mean BMI increased from 20.66 to 22.63 kg/m2 and the mean difference was 2.0 (2.0) whereas in women with BMI >23.0, the mean weight increased from 26.58 to 29.62kg/m2 and the mean difference is 3.0 (2.1).

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Table 4.3 Effects of Implanon on Body Mass Index (kg/m²) between two groups

Mean SD

Mean Difference

(95% CI)

T P value*

BMI

Categories N BMI at insertion (kg/m²)

BMI at removal ((kg/m²)

≤23.0 33 20.66(1.55) 22.63(2.77) 1.96

(2.65, 1.27) 5.80 0.001

>23.0 37 26.58(2.99) 29.62(4.22) 3.03

(3.73, 2.35) 8.94 0.001

*Paired t test

4.3 EFFECTS ON BLOOD PRESSURE

The effects of Implanon on SBP was statistically not significant in both BMI groups (P>0.05). The SBP increment was more in group of women with BMI >23.0 (Table 4.4).

Table 4.4 Effects of Implanon on Blood Pressure (SBP) between two groups

Mean SD

Mean Difference

(95% CI)

T P value*

BMI

Categories N

SBP at insertion (mmHg)

SBP at removal (mmHg)

≤23.0 33 115.27(14.15) 115.76 (12.45)

0.49

(4.89, 3.92) 3.92 0.82

>23.0 37 116.86(11.29) 121.59 (12.03)

4.73

(8.74, 0.72) 2.39 0.22

*Paired t test

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The DBP increment was more in group of women with BMI >23.0 and it was statistically significant (P<0.002) (Table 4.5).

In women with BMI ≤ 23.0, the mean DBP increased from 71.18 to 70.21/mmHg and the mean difference of 1.0 (13.1) was not significant (P>0.05) whereas in women with BMI >23.0, the mean DBP increased from 74.22 to 78.41/mmHg and the mean difference of 4.2 (7.6) was significant (P<0.05).

Table 4.5 Effects of Implanon on Blood Pressure (DBP) between two groups

Mean SD

Mean Difference

(95% CI)

T P

value*

BMI

Categories N DBP at

insertion

DBP at removal

≤23.0 33 71.18(8.32) 70.21(12.71) 0.97

(3.69, 5.63) 0.42 0.68

>23.0 37 74.22(7.92) 78.41(8.89) 4.2

(6.73, 1.65) 3.35 0.002

*Paired t test

4.4 BLEEDING PATTERN

All except 5 out of 70 (92.9%) of women demonstrated menstrual disturbance whilst on Implanon. Infrequent bleeding being the most common abnormal menses that women experienced which comprises 35.7%, followed by amenorrhoea, 30%.

However, the difference of menstrual disturbance between these two BMI groups using the Fisher’s Exact Test was not statistically significant

(P >0.05).

THE EFFECTS OF SUBDERMAL ETONORGESTREL ON BODY WEIGHT, BLOOD PRESSURE, MENSTRUAL

THE EFFECTS OF SUBDERMAL ETONORGESTREL ON BODY WEIGHT, BLOOD PRESSURE, MENSTRUAL

AND NON- MENSTRUAL ADVERSE EFFECTS BETWEEN TWO BMI GROUPS

BY

FAIZATUNNOR BT MUHAMAD

A thesis submitted in fulfilment of the requirement for the degree of Master of Obstetrics and Gynaecology

Kulliyyah of Medicine

International Islamic University Malaysia

DECEMBER 2016

ABSTRACT

APPROVAL PAGE

DECLARATION

INTERNATIONAL ISLAMIC UNIVERSITY MALAYSIA DECLARATION OF COPYRIGHT AND AFFIRMATION OF

FAIR USE OF UNPUBLISHED RESEARCH

THE EFFECTS OF SUBDERMAL ETONORGESTREL ON BODY WEIGHT, BLOOD PRESSURE, MENSTRUAL AND NON- MENSTRUAL ADVERSE EFFECTS BETWEEN TWO BMI

GROUPS

ACKNOWLEDGEMENTS

TABLE OF CONTENTS

LIST OF TABLES

LIST OF FIGURES

LIST OF ABBREVIATION

CHAPTER ONE INTRODUCTION

CHAPTER TWO LITERATURE REVIEW

CHAPTER THREE

RESEARCH METHODOLOGY

CHAPTER FOUR RESULTS