Biological effects of oral contraceptive steroids.

The addition of steroids causes alterations in many physiological processes as well as in the reproductive system. Since oral contraceptives (OCs) are synthetic steroids and structurally differnt they do not have exactly the same activity or metabolism as do natural steroids. The structures of 14 commonly used compounds are illustrated. The OCs are prescribed as combined or sequential regimens. Under the combined regimen 20 or 21 tablets each containing 1 or more synthetic progestins and estrogens are to be taken from Day 5 to Day 24 or 25 of each cycle. With the sequential regimen 15 or 16 tablets containing only estrogen are followed by 5 tablets containing progestin and estrogen. Withdrawal bleeding usually follows in both regimens within a few days. Medication is resumed on Day 5 of the new cycle. A 3rd regimen with continuous daily medications using small doses of progestins has been used. Combined type OCs are almost 100% effective in preventing pregnancy. The sequential regimen is slightly less effective. Data from a national survey in the U.S. indicates a continuation rate of 73% after 44 months of use. In several developing countries continuation has not been so high. The antifertility effectiveness of most contraceptive steroids is thought to be due to their ability to suppress ovulation by interference with the interactions of the hypothalamus and pituitary which result in the alterations of the secretion of gonadotropins. Recovery of fertility after discontinuing use of contraceptive steroids is usually rapid. Although congenital malformations of children subsequently born have not increased an excess of chromosomal abnormalities has been reported in spontaneously aborted embryos. Changes in the histology and enzymology of the endometrium have been described during treatment with OCs. Also alterations in cervical mucus occur. Carcinoma in situ of the cervix has been reported to be more frequent in OC users than in diaphragm users. Preliminary studies suggest that OC use may give some protection against breast cancer. Some OCs have been shown to reduce milk production in nursing women. Carbohydrate metabolism has been found to be modified by OC use. Lipid metabolism studies have shown a rise in serum triglyceride concentrations but not of cholesterol. Estrogens have been considered the cause of this rise. Liver functions are modified by OC use. Elevated blood pressure may result in 15% of previously normotensive women using OCs. This effect is reversible. Increasing plasma renin activity and higher renin substrate angiotensin have been found in these patients. Clotting mechanisms have been shown to be affected. Thromboembolic disease has been estimated to increased 3 or more times in OC users. Mortality from these causes has been estimated to be 7 times greater. A high estrogen content of the OC has been blamed.