What is the effect of oral contraceptives (OCs) on cortisol levels?

From the Guidelines

Oral contraceptives can increase cortisol levels in the body, primarily due to the estrogen component, which affects the body's stress response system by increasing the production of corticosteroid-binding globulin (CBG) in the liver. When women take combined hormonal contraceptives containing estrogen and progestin, these synthetic hormones can affect the body's stress response system. Specifically, oral contraceptives tend to increase the production of corticosteroid-binding globulin (CBG) in the liver, which is the protein that binds to cortisol in the bloodstream. This leads to higher total cortisol levels, though free (unbound) cortisol may not be significantly affected. The estrogen component is primarily responsible for this effect, with higher estrogen doses causing more pronounced increases in cortisol levels 1.

This elevation in cortisol is generally not clinically significant for most healthy women and doesn't typically cause symptoms of cortisol excess. However, women with conditions affected by cortisol levels, such as adrenal disorders or certain mood disorders, should discuss this potential effect with their healthcare provider. The impact varies between different contraceptive formulations, with lower-dose pills and progestin-only methods having less effect on cortisol levels than higher-dose combined pills.

Some key points to consider:

• The effect of oral contraceptives on cortisol levels is primarily due to the estrogen component.
• Higher estrogen doses cause more pronounced increases in cortisol levels.
• The impact of oral contraceptives on cortisol levels varies between different contraceptive formulations.
• Women with conditions affected by cortisol levels should discuss this potential effect with their healthcare provider.
• The evidence from recent studies, such as the 2024 guidelines of care for the management of acne vulgaris 1, supports the use of combined oral contraceptives for acne treatment, but also highlights the importance of considering the potential effects on cortisol levels.

In terms of morbidity, mortality, and quality of life, the benefits of oral contraceptives in reducing acne and improving quality of life outweigh the potential risks associated with increased cortisol levels for most healthy women. However, individual circumstances and medical histories should be taken into account when making decisions about oral contraceptive use.

From the Research

Effect of Oral Contraceptives on Cortisol Levels

• The use of oral contraceptives has been associated with changes in cortisol levels, with some studies suggesting an increase in cortisol levels due to the estrogen component of these contraceptives 2, 3, 4, 5.
• A study published in 2024 found that a woman taking a norgestimate-ethinyl estradiol contraceptive had an exaggerated increase in serum cortisol levels, which decreased after she stopped taking the contraceptive for 2 months 2.
• Another study from 1987 found that women taking a low-estrogen oral contraceptive had higher plasma-free and salivary cortisol levels compared to controls, as well as elevated corticosteroid-binding globulin (CBG) levels 3.
• A 2017 study found that women taking oral contraceptives had increased circulating cortisol levels, which were associated with alterations in glucocorticoid signaling and changes in phospholipid levels 4.
• A 2003 study found that four different oral contraceptives caused a significant increase in cortisol levels, which was related to the estrogen dose 5.

Mechanisms of Cortisol Level Changes

• The increase in cortisol levels associated with oral contraceptive use is thought to be due to the estrogen component, which can increase the levels of cortisol-binding globulin (CBG) 2, 3.
• The elevated CBG levels can lead to an increase in total cortisol levels, while the free cortisol levels may remain unchanged 2, 5.
• The changes in cortisol levels and glucocorticoid signaling associated with oral contraceptive use may have implications for the diagnosis and treatment of adrenal dysfunction and stress-related disorders 6, 4.

Clinical Implications

• The changes in cortisol levels associated with oral contraceptive use should be taken into account when interpreting cortisol levels in women taking these contraceptives 2, 3, 6.
• The use of salivary cortisol measurements may be a useful tool for diagnosing adrenal dysfunction in women taking oral contraceptives, as salivary cortisol levels are less affected by the estrogen component of these contraceptives 3, 6.
• Further research is needed to fully understand the effects of oral contraceptives on cortisol levels and glucocorticoid signaling, and to determine the clinical implications of these changes 4, 5.