Gracial ProdMonograph_cover - epgonline.org

Safety aspects
Gracial has a standard dose of EE (average of 33 µg/day) and
has demonstrated effects on hemostatic parameters
comparable to that of a classic triphasic regimen.
Initial confusion
Epidemiological data
In 1995 and 1996, new epidemiological data on the
association between Pill use and the risk of VTE became
available, which initially caused great confusion because they
were quite at variance with understanding of the issues at the
time (WHO 1995; Jick et al 1995; Spitzer et al 1996).
It was reported that OCs containing the same dose of 30 µg
EE were associated with different odds ratios for VTE
depending upon their progestogen component [levonorgestrel
(LNG), desogestrel (DSG) or gestodene (GSD)]. The odds ratio
of VTE in users of OCs containing DSG or GSD ranged between
1.5 and 2.2 compared to women using OCs containing LNG.
This finding was in contrast to the medical consensus from the
preceding 35 years of Pill research, in which the risk of VTE
had been shown to decline in parallel with reductions in the
EE dose, irrespective of the progestogen (RCGP 1974; Sartwell
et al 1969; Vessey et al 1977; Gerstmann et al 1991).
In the context of existing and new epidemiological data, it
appeared that the incidence of this venous complication in
women using a third-generation OC (a low dose of EE in
combination with either DSG or GSD) was approximately the
same as that in women using a second-generation OC (a low
dose of EE in combination with LNG) 10 years earlier.
Surprisingly, however, the incidence of VTE in the latter group
had reduced over time. It became clear that the observed
difference in risk of VTE between OC generations was due to a
reduction in the incidence of venous complications with the
second-generation Pills over time, rather than to an
unexpected increase with third-generation Pills.
Healthy user
effect
This decline in incidence of VTE over time has been attributed
to the so-called ‘healthy user’ effect (i.e. the selective removal
of high-risk persons from a cohort of users over time), which
has been operational with the introduction of each new oral
contraceptive (RCGP 1974, 1978; Jick et al 1995; WHO
1995; Gerstmann et al 1991; Vessey 1988; Lewis et al 1996).
In the group of women starting with the Pill, a certain
proportion is expected to have a not yet identified
predisposition to VTE. If these women develop VTE, they will
discontinue use of their OC as they become contraindicated.
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