Kelnor 1/50 (Page 3 of 8)

e. Persistence of Risk of Vascular Disease

There are three studies that have shown persistence of risk of vascular disease for users of oral contraceptives. In a study in the United States, the risk of developing myocardial infarction after discontinuing oral contraceptives persisted for at least 9 years for women 40 to 49 years old who had used oral contraceptives for 5 or more years, but this increased risk was not demonstrated in other age groups.¹⁶ Another American study reported former use of oral contraceptives was significantly associated with increased risk of subarachnoid hemorrhage.⁵⁷ In another study, in Great Britain, the risk of developing non-rheumatic heart disease plus hypertension, subarachnoid hemorrhage, cerebral thrombosis, and transient ischemic attacks persisted for at least 6 years after discontinuation of oral contraceptives, although the excess risk was small.^{14, 18, 66} It should be noted that these studies were performed with oral contraceptive formulations containing 50 mcg or more of estrogens.

2. Estimates of Mortality From Contraceptive Use

One study⁶⁷ gathered data from a variety of sources that have estimated the mortality rates associated with different methods of contraception at different ages (Table 2). These estimates include the combined risk of death associated with contraceptive methods plus the risk attributable to pregnancy in the event of method failure. Each method of contraception has its specific benefits and risks. The study concluded that, with the exception of oral contraceptive users 35 and older who smoke and 40 or older who do not smoke, mortality associated with all methods of birth control is low and below that associated with childbirth. The observation of a possible increase in risk of mortality with age for oral contraceptive users is based on data gathered in the 1970’s, but not reported until 1983.⁶⁷ However, current clinical practice involves the use of lower estrogen dose formulations combined with careful restriction of oral contraceptive use to women who do not have the various risk factors listed in this labeling.

Because of these changes in practice and, also, because of some limited new data that suggest that the risk of cardiovascular disease with the use of oral contraceptives may now be less than previously observed,^{48, 152} the Fertility and Maternal Health Drugs Advisory Committee was asked to review the topic in 1989. The Committee concluded that, although cardiovascular disease risks may be increased with oral contraceptive use after age 40 in healthy nonsmoking women (even with the newer low-dose formulations), there are greater potential health risks associated with pregnancy in older women and with the alternative surgical and medical procedures that may be necessary if such women do not have access to effective and acceptable means of contraception.

Therefore, the Committee recommended that the benefits of oral contraceptive use by healthy nonsmoking women over 40 may outweigh the possible risks. Of course, older women, as all women who take oral contraceptives, should take the lowest possible dose formulation that is effective.

Table 2. Annual number of birth-related or method-related deaths associated with control of fertility per 100,000 nonsterile women, by fertility control method according to age.⁶⁷

				Age
Method of control		15-19	20-24	25-29	30-34	35-39	40-44
No fertility control methods*		7.0	7.4	9.1	14.8	25.7	28.2
Oral contraceptives
	nonsmoker**	0.3	0.5	0.9	1.9	13.8	31.6
	smoker**	2.2	3.4	6.6	13.5	51.1	117.2
IUD**		0.8	0.8	1.0	1.0	1.4	1.4
Condom*		1.1	1.6	0.7	0.2	0.3	0.4
Diaphragm/spermicide*		1.9	1.2	1.2	1.3	2.2	2.8
Periodic abstinence*		2.5	1.6	1.6	1.7	2.9	3.6
* Deaths are birth-related ** Deaths are method-related Adapted from Ory.67

Adapted from Ory.⁶⁷

3. Malignant Neoplasms

Breast Cancer

Kelnor 1/50 is contraindicated in females who currently have or have had breast cancer because breast cancer may be hormonally sensitive (see CONTRAINDICATIONS).

Epidemiology studies have not found a consistent association between use of combined oral contraceptives (COCs) and breast cancer risk. Studies do not show an association between ever (current or past) use of COCs and risk of breast cancer. However, some studies report a small increase in the risk of breast cancer among current or recent users (<6 months since last use) and current users with longer duration of COC use (see POSTMARKETING EXPERIENCE).

Cervical Cancer

Some studies suggested that oral contraceptive use was associated with an increase in the risk of cervical intraepithelial neoplasia, dysplasia, erosion, carcinoma, or micro-glandular dysplasia in some populations of women.^{17, 50, 103-115} However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors.

In spite of many studies of the relationship between oral contraceptive use and breast and cervical cancers, a cause and effect relationship has not been established.