Vol. 26, No. 3, March 1975 Printed in U.SA.

FERTILITY AND STERILITY Copyright" 1975 The American Fertility Society

CLINICAL EXPERIENCE WITH ETHINYL ESTRADIOL AND D-NORGESTREL AS AN ORAL CONTRACEPTIVE RUBEN APELO, M.D., F.P.C.S.,

AND

IRMA VELOSO, M.D.

Reproductive Biology Center, Department of Obstetrics and Gynecology, College of Medicine and Philippine General Hospital, University of the Philippines, Manila, Philippines

Inman and Vessey, 1 Vessey and Doll2 and other researchers3-8 suggested a relationship between deaths and morbidity due to thromboembolism and the use of oral contraceptives. Notwithstanding a few reports to the contrary, 9- 11 the additional risk of death related to the use of oral contraceptives is estimated to be 1.3 to 2.9/100,000. 12 Tietze 13 considered this small risk to be probably no greater than the increased mortality associated with unwanted pregnancies. Nevertheless, it seems imperative to find out whether the currently available combination oral contraceptives can be improved, particularly in light of the findings of Inman et al 14•15 of a positive correlation between the dose of estrogen and the risk of thromboembolism. These researchers showed that the risk of pulmonary embolism was three times higher among women taking preparations with 100 J.Lg of estrogen than among women taking preparations with 50 J.Lg of estrogen. Furthermore, most metabolic side effects 16 (eg, fluid retention, hypertension, and carbohydrate and lipid metabolism alterations) and nausea 17 are estrogen. induced. This study investigates the efficacy and side effects of a combination oral contraceptive that contains a low level of estrogen.

Received June 7, 1974.

MATERIALS AND METHODS

Subjects. One hundred eighty-one sexually active women of proven fertility were studied in the Family Planning Clinic, Philippine General Hospital, Manila. Ages ranged from 18 to 42 years, with a median of 25 years. Body weights ranged from 31 to 64 kg (68 to 140 lb) with a mean of 46 kg (100.8 lb). The women had had one to ten pregnancies each (mean, 3.5). Coital frequency ranged from one per month to five per week (median, two per week.) The interval between last delivery and start of medication ranged from one to 48 months (median, eight weeks). All the women menstruated regularly. Pretreatment cycles lasted 25 to 32 days. The menses lasted two to seven days (mean, four days). The amount of menstrual flow was moderate in 85.1%, scanty in 6.6%, and heavy in 8.3% ofthe women. Home visits were arranged in order to determine why certain subjects failed to return for their monthly consultations. Dose. The oral contraceptive formulation consisted of 150 J.Lg d-norgestrel and 30 J.Lg ethinyl estradiol. Each patient received one tablet daily for 21 days and then received no tablets for the next seven days. The first treatment cycle was started on day 5 of the menstrual period. RESULTS

There were no pregnancies in 181 women during 1,488 cycles of treatment. One hundred and eleven women continued 283

284

March 1975

APELO AND VELOSO

the treatment for six to 12 cycles (median, nine cycles) until the study terminated. Seventy women dropped out after one to 11 cycles (median, three cycles); it was possible to follow up 36 of these. Seven of the dropouts discontinued taking the pill due to dizziness, dizziness and chest tightness, dizziness and headache, dizziness and nausea, dizziness and high blood pressure, weight loss, or weight loss and scanty menstrual flow. Twenty-nine women dropped out of the study for reasons not related to the drug (eg, two wished to have another baby, one died of lung cancer, one had asthma, and 25 found it inconvenient to go to the clinic or had moved to a distant province). Six dropouts were pregnant at the time of follow-up. All had the usual withdrawal bleeding after the last cycle of treatment, which indicated that pregnancy did not occur during treatment. Three were four to six months pregnant at the time of follow-up; onset of pregnancy was two to five months after discontinuation of treatment. One of these was one of the two who wanted another baby. The remaining three became pregnant one to two months after discontinuing treatment; one woman had an induced abortion at one month of gestation and two had spontaneous abortions at two months of gestation. Fifty-six patients missed one to five pills per cycle (median, two pills) in one or two cycles. The percent distributions of cycle duration, menstruation duration, and flow amount before and during treatment are shown in Table 1. Cycle duration during treatment was slightly shorter than that before treatment, but the duration was 25 to 32 days in 96.2% of treatment cycles. The duration of menstruation was three to five days in 93.2% of treatment cycles and the amount of flow was moderate in 87%. Menstruation began three to five

TABLE 1. Percent Distribution 8 of Cycle Duration, Menstruation Duration, and Menstrual Flow Amount Menstrual data

Cycle duration (days) 24 25-28 29-32 33-36 37-40 41-44 Menstruation duration (days) 1-2 3-5 6-7 8-12 Amount of menstrual flow Light Moderate Heavy

Before treatment During treatment

32.5 67.5

4.5 83.8 11.2 0.5

0.9 58.3b 37.9b 2.5b 0.2 0.2

4.1 93.2b 2.5b 0.2

~

6.6 85.1 8.3

8.8 87.0 4.2b

8 Percent of 1,488 cycles in 181 women. bSignificantly different from before treatment (P (0.9)

~

0

z

0

::o:l

ga

...,

00

gJ t"'

•All figures represent data volunteered bv oatient as well as those obtained by direct suggestive questioning, except the figures in parentheses which represent only incidence of symptoms volunteered by patient. bSignificantly different from pretreatment value (P

Clinical experience with ethinyl estradiol and d-norgestrel as an oral contraceptive.

One hundred eighty-one women received 30 mug of ethinyl estradiol plus 150 mug of d-norgestrel as an oral contraceptive for 21 days and then received ...
533KB Sizes 0 Downloads 0 Views