Oral contraceptive type and functional ovarian cysts Stephan F. Lanes, PhD: Brenda Birmann, BA: Alexander M. Walker, MD, DrPH:·b and Suanne Singer, BA c Chestnut Hill and Boston, Massachusetts, and Augusta, Maine OBJECTIVE: We tested the hypothesis that multiphasic, low-dose monophasic, and high-dose monophasic oral contraceptives share a common protective effect against functional ovarian cysts. STUDY DESIGN: We conducted a cohort study using the automatic files of Maine Medicaid to assemble a population of 7462 women between the ages of 15 and 44 who were prescribed an oral contraceptive between Jan. 1, 1987, and Dec. 31,1988. We included as cases 32 women with a principal diagnosis of a functional ovarian cyst confirmed by medical records as being > 20 mm in diameter. RESULTS: At comparison with the absence of an oral contraceptive prescription, we observed decreasing rates of functional ovarian cysts among women prescribed multiphasic pills (rate ratio 0.91, 95% confidence interval 0.3000 to 2.31), low-dose monophasic pills with :535 flog estrogen (rate ratio 0.52, 95% confidence interval 0.17 to 1.33), and high-dose monophasic pills with >35 ILg estrogen (rate ratio 0.24, 95% confidence interval 0.01 to 1.34). CONCLUSIONS: The protective effect of oral contraceptives against functional ovarian cysts reported previously for high-dose monophasic pills may be attenuated with newer pills of lower hormonal potency. (AM J QBSTET GVNECOl 1992;166:956-61.) Key words: Oral contraceptives, functional ovarian cys ts Oral contraceptives we re introduced in the United States in 1960, and the most popular formulations through the mid-1960s were combination pills contain- ing progestin and >50 estrogen." 2 Besides being remarkably effective at preventing pregnancy, these high-dose combination pills also conferred certain health benefits, such as reducing the risk of functional ovarian cysts. s " Publicity arose concerning possible ad- verse effects, however, and 1967 saw the introduction of low-dose formulations containing :535 flog estrogen. 1 Among the unintended effects of the early oral con- traceptives was an increased risk of thromboembolic disease, which epidemiologic studies suggested was re- lated to hormonal dose." Possibly as a result of mount- ing concern about adverse effects, the popularit y of the high-dose pills declined through the 1970s. I, 2 This trend continued into th e 1980s with the introduction in 1984 of multiphasic pills, which not onl y lowered hormone doses but also varied the dosage over the 21- day medication period in an attempt to mimic more closely the natural hormone cycle.' In 1987, Caillouette and Koehler' reported on seven women in their clinical practice who were diagnosed with functional ovarian cysts soon after starting to use a multiphasic contraceptive . The hypothesized relation between multiphasic pills and functional ovarian cysts From Epidemiolo gy Resources Inc." the Harvard S chool of Public Health/ and the Maine Health Information Center.' Supported in part by G.D. Searle & Co. Received f or publication June 4, 1991; revised September 3, 1991; accepted September 13, 1991. Reprint requests: Stephan Lanes, Epidemiology R e sources Inc., One Newton Executive Park, Newton, MA 02162. 6/1/33774 956 has biologic plausibility because multiphasic pills may not suppress ovarian function to the same degree as pills with higher hormone doses. 8 .10 Initial investigation by Grimes and Hughes" s howed that national trends in sales of multiphasic oral contraceptives were not cor- related with hospitalization rates for functional ovarian cysts. Such correlations are of limited use in investi- gating etiologic relations, however, and even though no relation was apparent , the investigators cautioned that "this indirect assessment can neither confirm nor refute the postulated association."" To date, there have been no measurements of the incidence of functional ovarian cysts among women using multiphasic oral contraceptives. We report here the rate of functional ovarian cysts associated with use of multiphasic pills, low-dose monophasic pills, and high-dose monophasic formulations of oral contracep- tives, and we contrast these rates with one another and with the rate of cysts associated with nonuse of oral contraceptives. Material and methods We used the automated files of Maine Medicaid to identify a cohort of 9461 women who were prescribed an oral contraceptive from Jan. I, 1987, to Dec. 31 , 1988. We used Medicaid claims data to exclude from the primary analyses women who were not of repro- ductive age , who had cancer or ovarian dysfunction, or who were given drugs that might interfere with hor- mone metabolism. These drugs included fertility drugs and hormones, antipsychotics, anticonvulsants, and an - titubercular drugs. After exclusions, the study popu- lation comprised 7462 women between the ages of 15