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Venous Thromboembolism and Anticoagulation
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
Combined estrogen-progestin oral contraceptives have been associated with higher efficacy than progestin only pills, but have the disadvantage of an increased risk of VTE. This risk has been attributed to the estrogen component. In women taking estrogen-containing oral contraceptives the risk of VTE increases 39-fold to 99-fold among those heterozygous for factor V Leiden and prothrombin G20210A mutations [126]. A meta-analysis of eight observational studies assessing the risk of VTE in women prescribed progestin-oral contraception showed no increased risk compared with non-users of hormonal contraception [127]. In a sub-analysis of women prescribed injectable progestins, there was a two-fold increase in thrombotic risk. The type of progestin might influence this risk, with newer progestins such as desogestrel, gestodene, and norgestimate associated with a greater risk than older ones such as levonorgestrel, lynestrenol, and noresthisterone [128–130]. The risk of VTE of the general population increases two- to three-fold in users of CEPCs (combined estro-progestin contraception) with norethisterone, levonorgestrel, or norgestimate, and of six-fold in users of CEPCs containing desogestrel, gestodene, drospirenone, or cyproterone acetate [131].
Effects of Low-Dose Oral Contraceptives on Fibrinolysis in Teenagers
Published in Pia Glas-Greenwalt, Fibrinolysis in Disease Molecular and Hemovascular Aspects of Fibrinolysis, 2019
Conflicting results concerning the effects of high-dose and low-dose oral contraceptives on the fibrinolytic system have been published.32 Furthermore, it has been claimed that patients developing thrombosis during use of oral contraceptives already have a defective fibrinolytic system.33 Some investigators have reported enhanced clot lysis in oral contraceptive users,34 while others found decreased in vitro fibrinolysis.35 However, most of the newer investigations with formulations containing less than 50 μg estrogen combined with levonorgestrel, lynestrenol, or the newer less androgenic progestogens show an increase in t-PA activity and a decrease of the amount of PAI-1 activity in plasma leading to an improvement of the fibrinolytic activity.12,14,16,18,19,36-38 In contrast to these results, it was recently proposed that the increase in fibrinolysis seen in women on OC containing 30 μg of estrogen may be due to eleveted levels of factor XII and prekallikrein without a corresponding increase in their natural inhibitors.39 In this study t-PA and PAI-1 activity did not change significantly. Decreased levels of histidine-rich glycoprotein may be another explanation for the improved fibrinolysis seen in women on OC.40
Gonadotropins and Sex Hormones
Published in Istvan Berczi, Pituitary Function and Immunity, 2019
The effect of widely-employed steroid contraceptive agents on the immune reactivity of mice and rats was evaluated. Three different progesterone (lynestrenol, norethindrone, or norethynodrel) were administered in combination with estrogen (mestranol) in minimal antifertility doses. All the steroid contraceptive agents reduced significantly the severity of allergic encephalomyelitis in rats, but had variable effects on the antibody response of mice to SRBC and on anti mouse erythrocyte autoantibody formation. There was no effect on the anti-SRBC response of rats. Treatments with contraceptive steroids, which were otherwise immunosuppressive, did not modify the response of mice to T-independent antigen.207
Effects of progestin-only contraceptives on the endometrium
Published in Expert Review of Clinical Pharmacology, 2020
Carlo Bastianelli, Manuela Farris, Vincenzina Bruni, Elena Rosato, Ivo Brosens, Giuseppe Benagiano
Back in 1982, Ludwig [41] pointed out that the effects of low dose progestational contraceptive agents not blocking ovulation, may be masked by the action of endogenous estrogens. In order to minimize this effect, he evaluated the endometrium of POP users by light and electron microscopy following long-term oral administration of NET, lynestrenol, and LNG. He also evaluated two injectable preparations: DMPA and norethisterone enanthate (NET-EN). A variety of parameters were examined: gland mitoses and tortuosity, pseudo-stratification, basal vacuolation, signs of secretion, stromal edema, pre-decidual reaction, and leukocytic infiltration. He made several general observations: in all cases the volume of the endometrium was reduced in relation to duration of treatment; no specific pattern could be attributed to individual preparations; there was an enlargement of venous vessels and, with time, there was a decrease in the size of the spiral arteries. Particularly noticeable were modifications in the glandular compartment: glands were reduced in number, their epithelium usually appeared atrophic and well-preserved glands coexisted with atrophic ones. Already after 2 months of exposure, no signs of secretory activity could be detected, but the presence of areas of pseudo-decidualization was a common finding. Initially, there was a focal infiltration of round nuclear cells, but they tended to disappear with time.
Overall and bleeding-related discontinuation rates of a new oral contraceptive containing 4 mg drospirenone only in a 24/4 regimen and comparison to 0.075 mg desogestrel
Published in Gynecological Endocrinology, 2021
Pedro-Antonio Regidor, Enrico Colli, Santiago Palacios
Efforts to further reduce the risk have also changed the progestin component over time. After introducing the first COCs (which included the progestins lynestrenol, and ethynodiol diacetate), new progestins like levonorgestrel were introduced in the 1970s, and gestodene and desogestrel (DSG) in the 1980s.