Results of a clinical study with low dose oral contraceptives investigation with triphasic and monophasic preparations containing levonorgestrel and ethynylestradiol
Matsumoto, S.; Sato, T.; Matsuyama, E.; Tamada, T.; Wagatsuma, T.; Honda, H.
Current Therapeutic Research 44(1): 165-177
1988
ISSN/ISBN: 0011-393X Document Number: 363605
Clinical study with oral contraceptives has started in Japan, which is the sole country where oral contraception is not allowed. There are many reasons why clinical studies have been delayed. The government of Japan does not approve of oral contraceptives, mainly because the general public's view of oral contraceptives centers on unclarified side effects and this view is clouded by the problematic side effects of the original oral contraceptives. During the period when Japan closed its doors to oral contraceptives, research and development in this field progressed remarkably in foreign countries. The hormone content was decreased to the minimally required level and was adjusted to a level comparable to the physiological cyclic pattern. With these approaches, an oral contraceptive that contains a low hormone dose causes less side effects, and presents nearly 100% efficacy is now available. We investigated the efficacy, cycle control, and incidence of side effects of a triphasic preparation (T) containing ethinylestradiol and levonorgestrel (SH B 264 AB), and monophasic preparation (M) with the 30-.mu.g ethinylestradiol plus 150-.mu.g levonorgestrel fixed-dose regime in six insititutes. The triphasic pill was given to 52 subjects (455 cycles) and monophasic pill given to 31 subjects (330 cycles). Pregnancy did not occur. In both groups, the duration of withdrawal bleeding and spotting were observed in 1.1% and 1.3%, respectively, in the T group, and in 2.1% and 1.2%, respectively, in the M group. The T group was superior to the M group in respect to the incidence of irregular bleeding, although hormone content was lower. This difference was observed in the first few cycles. Concerning side effects, a very small number of women complained of such subjective symptoms as nausea, malaise, and hot sensation. In the T group, contrary to our expectations, body weight increased by more than 4 kg in three subjects (6.8%) and by more than 2 kg in eight subjects (18.2%), but in the M group, body weight hardly increased. There was no increase in blood pressure nor any change in blood variables in general hemorrhage, coagulation, prothrombin time, liver function, urea nitrogen, electrocytes, blood sugar. Total cholesterol significantly increased from 70 mg/dl in a pretreatment cycle to 181 mg/dl during the fifth to eighth cycle of the T group, although this change was within the normal range. It is concluded that a triphasic preparation containing ethinylestradiol and levonorgestrel is a promising oral contraceptive pill and is easy to use. Because it has a reliable contraceptive effect, its cycle control is equal or superior to the conventional oral contraceptives and the incidence of side effects is low.