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HomeGynaecologyContraceptive pill link to stress responses – Danish study

Contraceptive pill link to stress responses – Danish study

Scientists say social activities like playing board games or singing songs reduced stress hormone ACTH levels in women not using birth-control pills, but the activities had no such effect on those who were using them, suggesting the medication may affect the body’s natural stress response – possibly due to their influence on hormone regulation.

Although women have been using contraceptive pills since the 1960s, the intricate ways in how these hormone-filled tablets interact with the body are not fully understood, reports SciTechDaily.

The scientists, led by a team from Denmark’s Aarhus University, conducted a study to examine the stress responses in 131 young women when having a blood sample taken. Participants included some who were taking birth control pills and others who were not.

Specifically, the researchers focused on measuring the levels of the stress hormone ACTH in their blood.

The study showed that 15 minutes of social activity after having a blood sample taken lowers stress hormone levels in those not on the oral contraceptive. In contrast, women on birth control pills do not experience any reduction in their ACTH levels.

To avoid causing any additional stress to the test subjects, a small intravenous catheter was inserted with the first blood sample. The researchers could then draw blood after the social activity without having to prick the women with a needle again.

The test subjects averaged 20.5 years. After the blood sample had been taken, they could join in one of six different group activities, like playing board games, getting to know each other in a group session, singing songs together, or attending a church service.

“Being with other people is one of the most effective ways of reducing stress. Our results are really important because they indicate that people who use birth control pills do not experience the same reduced stress hormone levels in social activities as people who do not use the pill,” said Michael Winterdahl, a visiting scholar at the Translational Neuropsychiatry Unit and last author of the article.

The study was published in Behavioural Brain Research.

Several competing hypotheses

The study differs from previous ones that have primarily focused on the stress hormone cortisol in extreme circumstances. In this particular study, the researchers measured the stress hormone ACTH, which changes significantly faster than cortisol. This makes it possible to observe and analyse rapid changes in the stress response.

While it is well known that birth-control pills affect the stress response, looking at the stress hormone ACTH in connection with a social activity is a new approach.

“By studying ACTH levels, we take another step towards understanding how the brain regulates stress, as ACTH acts as a neurotransmitter from the brain to the adrenal cortex, which produces cortisol. When we analyse ACTH levels, we can gain insight into the quick-response mechanism that controls the body’s reaction to stress,” said Winterdahl.

Birth-control pills can affect the hypothalamic-pituitary-adrenal (HPA) axis. As the name indicates, the stress signal travels from the hypothalamus in the brain through the pituitary gland, which releases ACTH, to the adrenal glands, which release cortisol.

The researchers still need a final explanation for why birth-control pill users do not experience the same reduction of stress hormone levels in connection with social activities as people who are not on the pill.

“There are several competing hypotheses… Our research has pushed us closer to an explanation that centres on the brain and the ACTH dynamics. The biochemistry is complex, but we are working on the assumption that the pills can suppress the body’s own production of progesterone,” said Winterdahl.

Progesterone is broken down into the hormone allopregnanolone, which is involved in a wide range of calming effects and can influence the stress response.

Differences between phases

The women in the study were all in different phases of their menstrual cycle, and results showed that the stress response in those not on the pill depended on where they were in their monthly cycle. The stress-reducing group activities had no effect on the ACTH levels of the women who were in the proliferative phase of their cycle – just after their period had ended and the body began producing hormones to get ovulation started.

“Progesterone levels are very low during the proliferative phase of a natural cycle. This leads to a minimal conversion of progesterone into the hormone allopregnanolone.

“Since allopregnanolone is important for activating the receptors that regulate the stress response, we don’t see a reduction in ACTH levels in women with a natural cycle who have just had their period,” added Winterdahl.

He said women were also generally more physically active during the proliferative phase, which could be seen as an adaption in which the stress response and behaviour change in step with the cycle.

In women using the birth control pills, the stress response is “disconnected”, meaning it cannot be adapted to a given situation.

Research still cannot explain exactly how this affects women. Additional investigation is therefore necessary to clarify the complex mechanisms involved in the correlation between hormone levels and the stress response.

“It’s also relevant to point out that birth control pills aren’t just contraceptives. There are different generations of the pill, each with its own chemical structure due to the hormones used, meaning the pills have different side-effect profiles. So it’s crucial that our experiments are reproduced with a larger and more diverse group of test subjects,” Winterdahl said.

Study details

Adrenocorticotropic hormone secretion in response to anticipatory stress and venepuncture: The role of menstrual phase and oral contraceptive use

Marie Vadstrup Pedersen, Line Mathilde Brostrup Hansen, Ben Garforth, Paul Zak and Michael Winterdahl.

Published in Behavioural Brain Research on 24 August 2023


Oral contraceptives (OCs) are primarily known for their effects on the reproductive system, but they can also impact the hypothalamic–pituitary–adrenal (HPA) axis. The present study aimed to compare plasma adrenocorticotropic hormone (ACTH) responses to the anticipatory stress of participating in a scientific experiment and venepuncture in OC users versus naturally cycling (NC) women, with a focus on variations throughout the menstrual cycle.

We recruited 131 young women (average age 20.5) and obtained blood samples to measure plasma ACTH concentrations immediately after venepuncture and again after 15 min of group activities designed to facilitate interpersonal attachment and stress-buffering.

ACTH levels decreased in 70% of all participants throughout the group activities. A two-way repeated measures ANOVA highlighted a significant interaction between time and OC use, indicating differential changes in ACTH levels during social interaction between OC users and NC women. Further, the post-hoc analysis revealed that a period of stress-buffering group activities significantly decreased ACTH levels in NC women during menstrual and secretory phases, but not during the proliferative phase. In contrast, OC users did not display a decrease during group activities, regardless of the phase.

This study underscores the influence of OC use on stress regulation, demonstrating that OCs not only modulate reproductive functions but also impact ACTH stress reactivity. Additionally, it emphasises the importance of considering hormonal contraceptive use and menstrual cycle phases when assessing female stress responses.


SciTechDaily article – Scientists Discover New Side Effect of Birth Control Pills (Open access)


Behavioural Brain Research article – Adrenocorticotropic hormone secretion in response to anticipatory stress and venepuncture: The role of menstrual phase and oral contraceptive use (Open access)


See more from MedicalBrief archives:


Contraceptive pills tied to depression – large Swedish study


No link between hormonal birth control and depression


Contraception with fewer hormones still effective – Philippines modelling study







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