Postgraduate Medicine
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Benefits and risks of oral contraceptive use R. Stan Williams MD To cite this article: R. Stan Williams MD (1992) Benefits and risks of oral contraceptive use, Postgraduate Medicine, 92:7, 155-171, DOI: 10.1080/00325481.1992.11701539 To link to this article: http://dx.doi.org/10.1080/00325481.1992.11701539
Published online: 17 May 2016.
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipgm20 Download by: [University of Saskatchewan Library]
Date: 14 June 2016, At: 21:29
-@CME credit article
Benefits and risks of oral contraceptive use
R. Stan Williams, MD
Downloaded by [University of Saskatchewan Library] at 21:29 14 June 2016
Preview Oral contraceptives do more than prevent pregnancy. Estrogen lowers the risk of ovarian cancer and cysts, and progestin lowers the risk of endometrial cancer. However, some agents may increase the risk of thromboembolism, hypertension, and coronary artery disease, and all interact with many other drugs. Dr Williams describes how to choose the best formulation for a particular patient and summarizes contraindications to even low-dose oral contraceptive therapy.
At present, more than 20 brand names and more than twice that number of formulations of oral contraceptives are available 1-a confusing array of drugs from which to choose. How effective each of these agents is at preventing pregnancy depends on three factors: inhibition of ovulation, change in endometrial growth and ovum receptivity, and reduction in receptivity of cervical mucus to sperm. 2 Because they are more than 99% effective/ oral contraceptives offer women the most reliable form of easily reversible contraception other than abstention from coitus. In developing new agents, researchers aim at maintaining or improving current contraceptive efficacy while reducing side effects and ensuring long-term safety. Two types of estrogen and several types of progestin are used in oral contraceptives. Estrogen and progestin interact, so the type and dose of each must be consid-
ered to achieve balance. In keeping with good therapeutic principles, prescribing physicians should select an agent that contains the lowest doses of both components while still offering contraceptive protection. Monophasic and multiphasic formulations of oral contraceptives are available. In monophasic formulations, the dose of both estrogen and progestin remains constant throughout the menstrual cycle. In multiphasic formulations, the progestin level varies with different phases of the cycle and, depending on the product, the estrogen level may change or remain constant. Because responses to steroid hormones differ, a woman must often try more than one agent to identify the oral contraceptive that meets her requirements.
Estrogen component Most of the newer oral contraceptives contain 30 to 35 f..Lg of
ethinyl estradiol, 1 an estrogen compound to which an ethinyl group is added to protect against inactivation by the liver. 4 Doses lower than 30 f..Lg are not practical if cycle control is to be maintained. Estrogen has a synergistic effect with progestin, which inhibits ovulation through suppression of luteinizing hormone and follicle-stimulating hormone by means of negative feedback to the pituitary. RISKS-All side effects of estrogen therapy, but especially thromboembolism and hypertension, are dose-dependent. However, many investigators believe that there is a threshold dose below which estrogen causes no statistically significant increase in risk for these side effects. The side effect of most concern is thromboembolism, 5 although the risk is considered minimal with use of today's lowdose oral contraceptives. Data from prospective studies of oral contraceptive use that have been in progress for more than a decade indicate that only women over age 35 who smoke are at increased risk of thromboembolism. 6 Because of the life-threatening nature of this problem, however, and the increased risk of thrombosis that accompanies surgery, current labeling by the Food and Drug Administration (FDA) 1
continued
VOL 92/NO ?/NOVEMBER 15, 1992/POSTGRADUATE MEDICINE • ORAL CONTRACEPTIVES
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Downloaded by [University of Saskatchewan Library] at 21:29 14 June 2016
Whether lactating mothers should use estrogen-containing oral contraceptives is still under debate, but the American College of Obstetrics and Gynecology and the American Academy of Pediatrics approve the practice.
cautions that all oral contraceptive users scheduled for an operation should stop taking these agents 4 weeks before and not resume taking them until 2 weeks after surgery. Women should also wait at least 4 weeks after childbirth before taking oral contraceptives. 1 Hypertension, apparently caused by increased levels of angiotensinogen in the blood, has also been reported with estrogen use. 7 Primarily, it appears to be triggered by use of high-dose (ie, ~50 J..Lg ethinyl estradiol) oral contraceptives. In a study comparing the effects of low-dose contraceptives containing norethindrone in women with a history of hypertension and in normotensive women, 8 changes in mean blood pressure values over baseline values were not statistically significant in either group after 3 to 24 months of use. If blood pressure does rise, it usually returns to normal within a few weeks after the oral contraceptive is discontinued. 9 The risk of stroke is also related to estrogen dose. In a large prospective study of nonhemorrhagic stroke in oral contraceptive users in the United Kingdom in the early 1970s (before lowdose agents were available), 10 13 strokes were noted during
156
39,400 patient-years of observation. Among users of low-dose (ie,
ISSN: 0032-5481 (Print) 1941-9260 (Online) Journal homepage: http://www.tandfonline.com/loi/ipgm20
Benefits and risks of oral contraceptive use R. Stan Williams MD To cite this article: R. Stan Williams MD (1992) Benefits and risks of oral contraceptive use, Postgraduate Medicine, 92:7, 155-171, DOI: 10.1080/00325481.1992.11701539 To link to this article: http://dx.doi.org/10.1080/00325481.1992.11701539
Published online: 17 May 2016.
Submit your article to this journal
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ipgm20 Download by: [University of Saskatchewan Library]
Date: 14 June 2016, At: 21:29
-@CME credit article
Benefits and risks of oral contraceptive use
R. Stan Williams, MD
Downloaded by [University of Saskatchewan Library] at 21:29 14 June 2016
Preview Oral contraceptives do more than prevent pregnancy. Estrogen lowers the risk of ovarian cancer and cysts, and progestin lowers the risk of endometrial cancer. However, some agents may increase the risk of thromboembolism, hypertension, and coronary artery disease, and all interact with many other drugs. Dr Williams describes how to choose the best formulation for a particular patient and summarizes contraindications to even low-dose oral contraceptive therapy.
At present, more than 20 brand names and more than twice that number of formulations of oral contraceptives are available 1-a confusing array of drugs from which to choose. How effective each of these agents is at preventing pregnancy depends on three factors: inhibition of ovulation, change in endometrial growth and ovum receptivity, and reduction in receptivity of cervical mucus to sperm. 2 Because they are more than 99% effective/ oral contraceptives offer women the most reliable form of easily reversible contraception other than abstention from coitus. In developing new agents, researchers aim at maintaining or improving current contraceptive efficacy while reducing side effects and ensuring long-term safety. Two types of estrogen and several types of progestin are used in oral contraceptives. Estrogen and progestin interact, so the type and dose of each must be consid-
ered to achieve balance. In keeping with good therapeutic principles, prescribing physicians should select an agent that contains the lowest doses of both components while still offering contraceptive protection. Monophasic and multiphasic formulations of oral contraceptives are available. In monophasic formulations, the dose of both estrogen and progestin remains constant throughout the menstrual cycle. In multiphasic formulations, the progestin level varies with different phases of the cycle and, depending on the product, the estrogen level may change or remain constant. Because responses to steroid hormones differ, a woman must often try more than one agent to identify the oral contraceptive that meets her requirements.
Estrogen component Most of the newer oral contraceptives contain 30 to 35 f..Lg of
ethinyl estradiol, 1 an estrogen compound to which an ethinyl group is added to protect against inactivation by the liver. 4 Doses lower than 30 f..Lg are not practical if cycle control is to be maintained. Estrogen has a synergistic effect with progestin, which inhibits ovulation through suppression of luteinizing hormone and follicle-stimulating hormone by means of negative feedback to the pituitary. RISKS-All side effects of estrogen therapy, but especially thromboembolism and hypertension, are dose-dependent. However, many investigators believe that there is a threshold dose below which estrogen causes no statistically significant increase in risk for these side effects. The side effect of most concern is thromboembolism, 5 although the risk is considered minimal with use of today's lowdose oral contraceptives. Data from prospective studies of oral contraceptive use that have been in progress for more than a decade indicate that only women over age 35 who smoke are at increased risk of thromboembolism. 6 Because of the life-threatening nature of this problem, however, and the increased risk of thrombosis that accompanies surgery, current labeling by the Food and Drug Administration (FDA) 1
continued
VOL 92/NO ?/NOVEMBER 15, 1992/POSTGRADUATE MEDICINE • ORAL CONTRACEPTIVES
155
Downloaded by [University of Saskatchewan Library] at 21:29 14 June 2016
Whether lactating mothers should use estrogen-containing oral contraceptives is still under debate, but the American College of Obstetrics and Gynecology and the American Academy of Pediatrics approve the practice.
cautions that all oral contraceptive users scheduled for an operation should stop taking these agents 4 weeks before and not resume taking them until 2 weeks after surgery. Women should also wait at least 4 weeks after childbirth before taking oral contraceptives. 1 Hypertension, apparently caused by increased levels of angiotensinogen in the blood, has also been reported with estrogen use. 7 Primarily, it appears to be triggered by use of high-dose (ie, ~50 J..Lg ethinyl estradiol) oral contraceptives. In a study comparing the effects of low-dose contraceptives containing norethindrone in women with a history of hypertension and in normotensive women, 8 changes in mean blood pressure values over baseline values were not statistically significant in either group after 3 to 24 months of use. If blood pressure does rise, it usually returns to normal within a few weeks after the oral contraceptive is discontinued. 9 The risk of stroke is also related to estrogen dose. In a large prospective study of nonhemorrhagic stroke in oral contraceptive users in the United Kingdom in the early 1970s (before lowdose agents were available), 10 13 strokes were noted during
156
39,400 patient-years of observation. Among users of low-dose (ie,
