58 Usha Verma and Neil Verma
antagonistic effect on the EE-induced rise on some coagulation and
inflammation markers such as factor VII activity and fragment 1 + 2 and also
it reduced the EE-dependent total and free protein S. This effect was not seen
with dienogest, which is an antiandrogenic progestin [145]. Therefore
estrogen-induced effect on coagulation is counteracted by the progestogens
with androgenic properties while nonandrogenic progestins will not have an
effect [145-147].
Based on a collective review of studies on the risk of venous thrombosis
in women who use combined oral contraceptives, it appears that the OCP
containing LNG and 30 μg of estrogen is the safest oral form of hormonal
contraception [132].
Progestogen-only pills cause only minor effects on coagulation and
fibrinolysis [144]. A systematic review that included 26 published articles did
not suggest an increase in odds for venous or arterial events with the use of
most progestin-only contraceptives [148].
Progestins and Risk of Breast Cancer
Progestins’ effect on the breast cells differs according to the progestin
type, dose and duration of use and the resulting balance between cell
proliferation and apoptosis [149, 150]. However, in hormonal contraceptives
progestins are usually combined with EE and the effect on breast tissue depend
on a balance of both hormones. Different progestins have variable effect on
proliferation of breast cells. In a study conducted in surgically postmenopausal
cynomolgus monkeys conjugated equine estrogen (CEE) plus
medroxyprogesterone acetate induced a diffuse epithelial proliferation in the
mammary glands but the combination of Ethinyl estradiol and norethindrone
acetate did not cause the proliferation of the cells [151]. In another study
Conner et al. obtained fine needle biopsy specimens from mammary glands of
women using estradiol (2 mg) or estradiol valerate 2 mg plus norethindrone
acetate (1 mg) or dinogestrel (2 mg). In the study Ki67, used as a proliferation
marker, did not differ significantly between norethindrone or dinogestrel
groups, although the dinogestrel group showed a tendency for a weaker
proliferation [152].
The Million women study published in Lancet Journal in 2003 reported
that hormone replacement therapy in postmenopausal women is associated
with an increased risk of incident and fatal breast cancer. The incidence was
significantly increased in women taking estrogen-progestagen combinations