- Human pathology

Home > D. General pathology > Therapy, Toxics and drugs > oral contraceptives

oral contraceptives

Monday 23 March 2009

Estrogens, alone or in combination with progestin, have been widely used for over 35 years as oral contraceptives or as hormone replacement therapy by perimenopausal and postmenopausal women. Most oral contraceptives combine synthetic ethinyl estradiol or mestranol with a progestin or use progestin alone; hormone replacement therapy uses natural estrogens alone or in combination with progesterone. Recent epidemiologic evidence has clarified the potential benefits and risks of these widely used drugs.

Oral Contraceptives. There has been considerable concern and controversy about the safety of oral contraceptives, especially in relation to breast cancer. Two population-based, case-control studies, the Cancer and Steroid Hormone Study published in 1986 and the Women’s Contraceptive and Reproductive Experiences Study published in 2002, explored the association between past or current use of oral contraceptives and breast cancer.

The most recent study included women between ages 35 and 64 diagnosed with breast cancer between 1994 and 1998. Potential effects of duration, formulations containing a high dose of estrogen, and family history of breast cancer were compared in women diagnosed with breast cancer or in control women without cancer. Past or current use of oral contraceptives was not found to be associated with an increased risk of breast cancer in white or black women in the United States.

Previous studies of other hormone-responsive cancers have also shown no increased risk of cancer; in fact, oral contraceptive use was found to decrease the risk of endometrial and ovarian cancers. In contrast, women infected with human papillomavirus have an increased risk of developing cervical cancer if they use oral contraceptives, although this risk may be related to other lifestyle factors.

Uncommon adverse effects of oral contraceptives include:
Venous thrombosis and pulmonary embolism. Oral contraceptives increase the risk of thrombosis; this risk is higher in carriers of mutations in factor V or prothrombin.

The older, high-dose preparations incurred a greater risk, but a smaller risk persists even with the low-estrogen-containing oral contraceptives. The newer, third-generation oral contraceptives that combine low-dose estrogen with synthetic progestins confer an even higher risk.
Cardiovascular disease.

Estrogens and progestins have opposing effects on high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels. The overall effect on lipoproteins depends on the preparations used, especially the dose of progestin in the formulation.

Recent epidemiologic evidence suggests that nonsmoking healthy women younger than age 45 who use the newer low-estrogen formulations do not have an increased risk of atherosclerosis or myocardial infarction. However, the risk of myocardial infarction is increased in women older than age 35 who smoke. The risk of ischemic stroke is also increased, regardless of age or smoking history.

Liver tumors. Benign hepatic adenomas may occur, especially in older women who have used oral contraceptives for prolonged periods. These humans may rupture and cause intra-abdominal bleeding.