RANDOMISED DOUBLE-BLIND TRIAL OF FOUR ORAL PROGESTAGEN-ONLY CONTRACEPTIVES

Abstract

307 women in Ljubljana, Yugoslavia, took part in a randomised double-blind trial of four progestagen-only oral contraceptives (megestrol acetate 0·7 mg., norethisterone acetate 0·3 mg., chlormadinone acetate 0·5 mg., norgestrel 0·075 mg.). Each woman was followed up for a year or until treatment was discontinued. A fifth group of 71 women received a combined oral contraceptive ('Nuvacon'; ethinyl oestradiol 0·1 mg., megestrol acetate 2 mg.). Pregnancy-rates were 2 per 100 woman-years for norethisterone acetate (1 pregnancy) and norgestrel (1 pregnancy), 4 for chlormadinone acetate (2 pregnancies), and 13 for megestrol acetate (6 pregnancies). All but 2 of these pregnancies were in the first six months of trearment and all were classed as method failure. 1 patient who took her tablets irregularly became pregnant on nuvacon. None of the four progestagens provided such satisfactory cycle control as nuvacon, and menstrual disturbances caused a considerable number of women in all four progestatigen-trated groups to withdraw. Norgestrel was the most unsatisfactory preparation in this respect and norethisterone acetate the least. Apart from menstrual disturbance, over 60% of women were entirely free from side-effects throughout the trial. The use of norethisterone acetate was associated with the lowest pregnancy-rate, the lowest discontinuation-rate for menstrual disturbances and for other side-effects, the smallest proportion of short cycles, the least variation in cycle lenght, and the gratest proportion of women without side —effects, and emerges as the most promising of the four progestagens studied in this trial. Indeed, norethisterone acetate was found to be as acceptable as the combined oral contraceptive nuvacon. It no longer seems likely that any currently available progestagen will be found to prevent conception effectively without interfering to some extent with the hormonal control of the menstrual cycle.