One of the most common combined oral contraceptive pills has a negative impact on women's quality of life but does not increase depressive symptoms. This is shown by a major randomised, placebo-controlled study conducted by researchers at Karolinska Institutet in Sweden in collaboration with the Stockholm School of Economics. The results have been published in the scientific journal Fertility and Sterility.

"Despite the fact that an estimated 100 million women around the world use contraceptive pills we know surprisingly little today about the pill's effect on women's health. The scientific base is very limited as regards the contraceptive pill's effect on quality of life and depression and there is a great need for randomised studies where it is compared with placebos," says professor Angelica Lindén Hirschberg at the Department of Women's and Children's Health at Karolinska Institutet.

She has led just such a study together with Niklas Zethraeus, associate professor at the Department of Learning, Informatics, Management and Ethics, Anna Dreber Almenberg from the Stockholm School of Economics, and Eva Ranehill of the University of Zürich. 340 healthy women aged between 18 and 35 were treated randomly over the course of three months with either pills with no effect (placebos) or contraceptive pills containing ethinylestradiol and levonorgestrel, the most common form of combined contraceptive pill in Sweden and many other countries. Neither the leaders of the experiment nor the subjects knew which treatment was given to which women.

The women who were given contraceptive pills estimated their quality of life to be significantly lower than those who were given placebos. Both general quality of life and specific aspects like mood/well-being, self-control and energy level were affected negatively by the contraceptives. On the other hand, no significant increase in depressive symptoms was observed.

Since the changes were relatively small, the results must be interpreted with a certain amount of caution, the researchers emphasise. In the case of individual women, however, the negative effect on quality of life may be of clinical importance.

"This might in some cases be a contributing cause of low compliance and irregular use of contraceptive pills. This possible degradation of quality of life should be paid attention to and taken into account in conjunction with prescribing of contraceptive pills and when choosing a method of contraception," says Niklas Zethraeus.

The type of combined contraceptive pill that was used in the study (etinylestradiol + levonorgestrel) is recommended in many countries as the first choice since it is considered to entail the least risk of thrombosis among the combined contraceptive pills. The findings from the study cannot be generalised to other kinds of combined contraceptive pills because they may have a different risk profile and side-effects.

The study was supported by research grants from Jan Wallander and Tom Hedelius Foundation, Knut and Alice Wallenberg Foundation, Swedish Council for Working Life and Social Research, the Swiss National Science Foundation, the Swedish Research Council, Karolinska Institutet, and the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet.

Niklas Zethraeus, Anna Dreber, Eva Ranehill, Liselott Blomberg, Fernand Labrie, Bo von Schoultz, Magnus Johannesson, Angelica Lindén Hirschberg.
A first choice combined oral contraceptive influences general well-being in healthy women - a double-blind, randomized, placebo-controlled trial.
Fertility and Sterility, doi: 10.1016/j.fertnstert.2017.02.120.