Study finds plasma oxytocin levels higher in OC users

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Plasma oxytocin levels are significantly higher in oral contraceptive (OC) users than in to non-users, according to a study in Scientific Reports. The cross-sectional study of nearly 200 women also found that scores for satisfaction with life were higher among OC users.

“Most women have used oral contraception at some point in their lives, and they face an increased risk for developing depression,” said principal investigator Michael Winterdahl, PhD, an associate professor of clinical medicine at Aarhus University in Denmark.

“However, there have been very few studies about the mechanisms by which these pills can affect women's health and mood.”

Dr. Winterdahl told Contemporary OB/GYN that the oxytocin system is of particular interest because it mediates both reproductive physiology and social behavior.

The study comprised 185 young women, whose average age was 21.2 years. Women were divided into two cohorts: oral contraceptive users (n = 71) and non-users (n = 114).

A blood sample was obtained from all participants to test the plasma levels of oxytocin, adrenocorticotropic hormone (ACTH), estradiol, progesterone and testosterone.

Two datasets were collected as part of two separate studies in different cohorts of participants. The samples obtained in the second cohort were processed using improved methodology that assayed oxytocin from plasma using a RadioImmunoAssay (RIA) kit.

The oxytocin assay also included an extraction step to reduce binding of side products. Samples from the older dataset were also analyzed using a RIA kit; however, without an extraction step.

“Because our methodology for measuring oxytocin had improved between the two data collections, we were unable to pool the data,” Dr. Winterdahl said. “The two methods for measuring oxytocin, however, consistently revealed a significant difference between oral contraceptive users and non-users.”

Both datasets showed highly significant differences between users and non-users, with the former exhibiting elevated basal oxytocin and lower adrenocorticotropic hormone (ACTH), estradiol, progesterone and testosterone.

For instance, in the newer dataset, on average there was a 144 % higher oxytocin concentration in plasma in birth control users compared to non-users, whereas the older dataset only revealed a 24 % higher oxytocin concentration.

“The difference in percentages reflected our improved methodology for measuring oxytocin,” Dr. Winterdahl said.

Plasma hormone levels were also compared to self-reported measures of mood, well-being and depression. Satisfaction With Life Score (SWLS) was significantly higher in OC users than in non-OC users. However, there were no differences in the Beck Depression Score (BDI) and Positive and Negative Affect Schedule (PANES) between the two groups.

“We expected estrogens in birth control to raise oxytocin levels in plasma, and this indeed was the case,” Dr. Winterdahl said.

“But we were surprised that birth control users had higher scores for quality of life. Birth control users who suffer adverse effects tend not to sign up for scientific studies, and our sample consisted of young women in their early 20s, who probably were happy not having to worry about becoming pregnant.

Also, subjects with clinical depression were excluded from the study.”

The lack of information about the duration and the specific OC formulations used by the women were limitations as well. Menstrual cycles may have also affected the results because peripheral oxytocin levels increase during the menstrual cycle until ovulation and then decrease until menstruation begins again.

Despite these caveats, Dr. Winterdahl said changes in oxytocin may explain how birth control can affect mood.

“We anticipate that our research can critically advance our understanding of how changes in sex hormones increase susceptibility for depressive episodes, thus eventually providing novel preventive and therapeutic opportunities,” he said.


  1. Garforth, B., Degnbol, H., Terris, E.T. et al. Elevated plasma oxytocin levels and higher satisfaction with life in young oral contraceptive users. Sci Rep 10, 8208 (2020).
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