The thrombogenicity of the dienogest/estradiol valerate-containing oral contraceptive (Qlaira®)

During use of the combined oral contraceptive, there is a 3-6 times increased
risk of venous thrombosis. The dose of estrogen and the type of progestagen are
influencing this risk. The increased risk of venous thrombosis during use of a
combined oral contraceptive can be (partly) biologically explained by a by the
pill induced increased resistance of Activated Protein C (APC). An increased
resistance for the anticoagulant action of APC is a risk factor of venous
thrombosis.
In the past, research showed that combined oral contraceptives with a higher
risk of venous thrombosis induce a higher APC-resistance than low-risk combined
oral contraceptives.
Sex Hormone Binding Globuline (SHBG) is a transport protein which transports
estrogen and testosterone, and has a higher concentration in blood during use
of combined oral contraceptives. In various investigations, SHBG showed to be a
marker for the risk of venous thrombosis during use of combined oral
contraceptives as well.
The risk of venous thrombosis during use of the recently developed combined
oral contraceptive with dienogest/estradiolvalerate (Qlaira®) is not
investigated yet.

To measure APC resistance and SHBG levels as indicators of the risk of venous
thrombosis during use of the new developed combined oral contraceptive
containing dienogest/estradiolvalerate (Qlaira®) compared with a combined oral
contraceptive containing levonorgestrel/ethinylestradiol (Microgynon-30®).

80 healthy, voluntarily, female persons will be randomized in two groups. The
study is not blinded. The first group will use dienogest/estradiolvalerate
(Qlaira®) and the second group will use levonorgestrel/ethinylestradiol
(Microgynon-30®) as combined oral contraceptive. The contraceptives will be
provided by the investigators.
Before the subjects start to use the contraceptives, they have to fill in a
survey, and a blood sample will be taken. The contraceptives will be used for
three months. In the third month, four blood samples will be taken at day 2, 7,
24 and 26 of the cycle. This is one blood sample per phase of the fourphase
oral contraceptive dienogest/estradiolvalerate (Qlaira®). We*ll also take blood
samples of the users of levonorgestrel/ethinylestradiol (Microgynon-30®) at the
same days, as comparison.
At the last appointment, the subjects have to fill in a survey again. After
these three months, the investigation ends for the subjects.
We*ll measure all the determinants in the blood samples.

ienogest/estradiolvalerate-containing combined oral contraceptive or a
levonorgestrel/ethinylestradiol-containing combined oral contraceptive

The subjects have to visit the Leiden University Medical Centre (LUMC) five
times for the take of blood samples. Two times during these visits, they also
have to fill in a survey. The total time in the LUMC is maximal 60 minutes.
Taking blood is minimal invasive and doesn't have a lot of risks. There could
be a complication, like a hematoma or pain at the prick spot, but these
complications are temporary and don't give any healthrisks. Another risk are
the known side-effects of oral contraceptives as described by the WHO and Dutch
Society of Gynaecologists.