Contraception
Conditions
Keywords
Estetrol-drospirenone, Ethinylestradiol-levonorgestrel, Combined oral contraceptives, Arterial risks, Metabolic risks
Brief summary
The goals of this clinical trial are to investigate the effect of the estetrol (E4)-drospirenone combined oral contraceptive (COC) pill on flow-mediated dilatation (FMD) of the brachial artery and pulse wave velocity (PWV), in comparison to the ethinylestradiol (EE)-levonorgestrel COC pill, and to compare their respective effects on blood pressure, chronic inflammatory markers, as well as glycaemic and lipid indices. The main questions it aims to answer are: Does E4-drospirenone COC have significantly smaller effects then EE-levonorgestrel COC on FMD, PWV, blood pressure, chronic inflammatory markers, as well as glycemic and lipid indices. Researchers will compare E4-drospirenone to EE-levonorgestrel to see if the former has lower arterial vascular and metabolic risks. Participants will: * be randomised to take E4-drospirenone or EE-levonorgestrel COC pill according to product insert; * visit the clinic at baseline and 6 and 12 months post-recruitment for checkups and tests
Detailed description
Objectives: (1) To investigate the effect of the estetrol (E4)-drospirenone combined oral contraceptive (COC) pill on flow-mediated dilatation (FMD) of the brachial artery and pulse wave velocity (PWV), in comparison to the ethinyl-estradiol (EE)- levonorgestrel COC pill. (2) To investigate the effect of the E4-drospirenone COC pill on blood pressure, chronic inflammatory markers, as well as glycaemic /lipid indices. Hypothesis to be tested: E4-drospirenone has non-significant effect on FMD and PWV, as well as on blood pressure, chronic inflammatory markers, glycaemic and lipid profile compared to EE-levonorgestrel. Design and subjects: Open-label randomised controlled trial. Women (n=98) who are commencing COC pills for contraception or treatment of gynaecological conditions will be recruited. Study instruments: FMD, carotid-femoral and brachial-ankle PWV, blood pressure, serum high-sensitivity C-reactive protein and interleukin-6 measurements, glycaemic and lipid profile Interventions: (1) E4 15mg + drospirenone 3mg versus (2) EE 30mcg + levonorgestrel 150mcg Main outcome measures: FMD, carotid-femoral and brachial-ankle PWV Data analysis: Data will be analysed with both intention to treat and per protocol approaches. The primary and secondary outcome measures (continuous variables) at baseline and at 6 and 12 months after treatment will be compared by paired t-test (with logarithmic transformation of significantly skewed data). Changes in these parameters will be compared between the two study groups by linear mixed models. P values of \<0.05 will be considered statistically significant. Expected results: E4-drospirenone induces insignificant changes in FMD, PWV as well as blood pressure, chronic inflammatory markers, and glycaemic and lipid profile.
Interventions
DRUGEstetrol-drospirenone
Estetrol 15mg + drospirenone 3mg
DRUGEthinylestradiol-levonorgestrel
Ethinylestradiol 30mcg + levonorgestrel 150mcg
Sponsors
Dr. Hang Wun Raymond Li
The Family Planning Association of Hong Kong
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
* Aged between 18 and 49 years inclusive * Considering to use the COC pill for contraception or treatment of menstrual disorders
Exclusion criteria
* Being diagnosed with menopause * Having contraindications to COC, including (but not confined to) hypertension, diabetes mellitus with complications, history of ischaemic heart disease, thromboembolism, stroke, severe liver disease, oestrogen-sensitive cancers, undiagnosed abnormal uterine bleeding, smokers aged 35 years or above, or having body mass index \>=35 kg/m2 * Planning to get pregnant in the coming 1 year * Having been pregnant in the past 3 months * Having been on COC or hormone replacement therapy in the past 3 months (those who had been on these agents can stop these for 3 months as wash-out period before being recruited; this concurs with other similar studies in the literature) * Having been on anti-hypertensive, anti-diabetic or lipid-lowering agents in the past 3 months * Refusal to randomization
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Flow-mediated dilatation (FMD) | 0, 6 and 12 months | Flow-mediated dilatation of the brachial artery |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pulse wave velocity (PWV) | 0, 6 and 12 months | Pulse wave velocity (carotid-femoral and brachial-ankle) |
| Body mass index | 0, 6 and 12 months | Body mass index |
| Waist-hip ratio | 0, 6 and 12 months | Waist-hip ratio |
| Blood pressure | 0, 6 and 12 months | Blood pressure (systolic and diastolic) |
| Sex hormone-binding globulin | 0, 6 and 12 months | Serum sex hormone-binding globulin level |
| High sensitivity C-reactive protein | 0, 6 and 12 months | Serum high sensitivity C-reactive protein level |
| Fasting glucose | 0, 6 and 12 months | Fasting plasma glucose |
| 2-hour glucose | 0, 6 and 12 months | Plasma glucose at 2 hours after 75g oral glucose tolerance test |
| Haemoglobin A1c | 0, 6 and 12 months | Haemoglobin A1c |
| Fasting insulin | 0, 6 and 12 months | Serum fasting insulin level |
| Lipid profile | 0, 6 and 12 months | Lipid profile (low density lipoprotein cholesterol, high density lipoprotein cholesterol, triglycerides) |
Contacts
CONTACTRaymond HW Li, MD, FRCOG
CONTACTJennifer KY Ko, MBBS, FRCOG
PRINCIPAL_INVESTIGATORRaymond HW Li, MD, FRCOG
The University of Hong Kong
Outcome results
None listed