Benefits and risks of third-generation oral contraceptives

Abstract

OBJECTIVE:To evaluate the risks and benefits of thirdgeneration oral contraceptives. DATA SOURCES: When used consistently, oral contraceptives are a highly effective means of birth control. However, some women discontinue their use because of bothersome side effects such as acne, hirsutism, and weight gain. Oral contraceptives adversely affect thrombolysis, carbohydrate metabolism, and lipid profiles, and this may be why they have been associated with an increased risk of myocardial infarction and stroke in case-control and cohort studies. 1-4 Because these minor and major side effects have been correlated with the androgenicity of the progestin, third-generation oral contraceptives were created to decrease the amount of androgenic activity. They contain only low doses of estrogen ( Յ 35 g of ethinyl estradiol) combined with either desogestrel, norgestimate, or gestodene (gestodene is not FDA-approved for use in the United States), which are progestins with low androgenic activity (Table 1). Although they appear to be as effective as previous oral contraceptives and have a decreased incidence of side effects, they have been associated with an increased rate of venous thromboembolism. This prompted some regulatory agencies and professional groups to recommend restricting the prescribing of thirdgeneration oral contraceptives, but others contend that the data are not convincing enough to limit their use. This article will review the risks and benefits of third-generation oral contraceptives. METHODSA MEDLINE search of articles published from 1985 to 1998 was performed. The terms oral contraceptives , desogestrel , third-generation oral contraceptives , gestodene , and norgestimate were combined with the terms thromboembolism , myocardial infarction , cerebrovascular disorders , adverse effects , and stroke . English language articles containing original data on the association between thirdgeneration oral contraceptives and thromboembolism or cardiovascular disease were reviewed by both authors. Studies on the side effects of third-generation oral contraceptives and editorials on the controversy surrounding the relation between third-generation oral contraceptives and venous thrombosis, myocardial infarction, and stroke were also evaluated. In addition, references of articles were reviewed for other studies not identified by the MED-LINE search. All published studies containing original data on the relation between third-generation oral contraceptives and thromboembolic disease, myocardial infarction, or stroke are included in this review.

Risk Factors for Heart Attack, Stroke, and Venous Thrombosis Associated With Hormonal Contraceptive Use

“…Other studies have shown an increased risk of MI for older COC users and smokers. 66,67,[69][70][71][72] The mortality attributable to COC use among smokers younger than age 35 is 1 per 100 000. The mortality rate significantly increases to 1 per 7000 for smokers older than 35 years of age.…”

Contraception in women with obesity with special reference to gastric bypass surgery

“…The main risk was initially thought to be related to the oestrogen component and therefore various progestins were developed so that the oestrogen doses in COCs could be reduced (23). Apart from a wish to minimise these major side effects of COCs, there was also an attempt to decrease the level of androgen activity of the progestins, which led to the development of a third generation of COCs (24,25). The aim was to reduce the minor side effects of progestins, such as acne, hirsutism, and weight gain.…”

The other side of progestins: effects in the brain

“…These new progestins, beside having a strong progestational action, also exert anti-estrogenic, antigonadotropic, and antimineralocorticoid effects (Africander et al 2011). Among these, there are the third-generation progestins (desogestrel or gestodene), derived from LNG group, developed to decrease androgenic activity (LeBlanc & Laws 1999), and the fourth-generation progestins. In this latter group, nomegestrol acetate exhibits partial anti-androgenic activity (Lello 2010, Van Diepen et al 2011) DNG, DRSP, and trimegestone have a significant anti-androgenic activity, whereas nestorone has no activity via the AR (Fotherby 1990, Philibert et al 1999, Schindler et al 2003.…”