Lavender essential oil and oral contraceptives

Mood Disorders Associated with COCs: A Clinical Trial Explores the Role of Lavandula angustifolia

There is a specific reason why many women stop taking the pill. It is not always a matter of efficacy or convenience: often, it is mood. Irritability, sadness, and a widespread sense of emotional heaviness that emerges during the weeks of use and that clinical guidelines still struggle to address satisfactorily.

A clinical trial published in 2024 in BMC Complementary Medicine and Therapies chose to start from this concrete issue, investigating whether a well-characterized natural extract,  orally administered Lavandula angustifolia essential oil, could make a difference in this specific population.

The underlying issue: how COCs influence mood

Combined oral contraceptives (COCs) act on the hormonal axis with effects that go far beyond ovulation suppression. Synthetic estrogens interfere with vitamin B6 synthesis, reducing the availability of neurotransmitters such as serotonin and norepinephrine. Second-generation progestins, such as levonorgestrel, increase monoamine oxidase levels, further depressing available serotonin.

The result is a real neurobiological substrate that may manifest as depressive states, irritability, and reduced mood tone. This is not a rare effect: in the United States, one study found that 86% of women using COCs had discontinued or changed therapy specifically because of negative mood-related effects.

Why lavender, and why in capsules

The choice of lavender was not accidental. Preclinical and clinical literature had already documented for years the activity of its main component, linalool, on the central nervous system. This volatile monoterpene inhibits voltage-dependent calcium channels, binds to NMDA receptors and serotonin transporters (SERT), and suppresses glutamate binding in the cerebral cortex.

Compared to aromatherapy, oral administration in standardized softgel capsules brings lavender closer to the nutraceutical supplement model, with clear advantages in terms of reproducible dosage and compliance. The formulation used in the study contained linalyl acetate (35.55%), 1,8-cineole (37.95%), limonene (13.04%), and linalool (8.96%), extracted through hydrodistillation from L. angustifolia, with a daily dose of 80 mg.

How the study was conducted

The trial adopted a two-parallel-group, placebo-controlled, triple-blind design: participants, researchers, and data analysts were all blinded to treatment allocation. Sixty women between 15 and 49 years of age, all COC users and characterized by predominantly negative affectivity, were recruited from 26 healthcare centers in Tabriz (Iran).

The intervention group received one 80 mg LEO capsule daily for 56 days; the control group received an identical placebo capsule. Psychological evaluations were conducted at baseline, day 28, and day 56 using the PANAS questionnaire for mood and the DASS-21 for stress, anxiety, and depression.

The results: mood, stress, and depression

The data showed statistically significant differences between the two groups across multiple dimensions.

Positive mood increased in the treated group, with a mean difference of 4.5 points versus placebo at 28 days (p=0.001) and 5.9 points at 56 days (p<0.001). Negative affectivity decreased by 3.5 points at 28 days and by 4.3 points at 56 days.

Regarding stress, the mean differences versus placebo were approximately 5 points at both time points (p<0.001). Depression also showed significant reductions: approximately 3 points difference at both 28 and 56 days (p=0.003 and p=0.002 respectively).

Anxiety was the only variable for which LEO did not produce a significant between-group difference, despite showing intra-group improvement. The authors hypothesize that this may depend on the baseline profile of the sample, excluding subjects with severe anxiety, or on differences in the type of extract compared to other studies.

An important safety point not to overlook

For those working on the development of formulations intended for women undergoing hormonal therapy, one detail from the literature deserves emphasis: previous studies have shown that lavender oil at a dose of 160 mg/day does not interfere with the contraceptive efficacy of COCs. This represents an important safety consideration for the positioning of any product within this segment.

What this means for nutraceutical formulators

This study provides a concrete insight for those developing nutraceutical products in the area of female psychological well-being. The target is specific and clinically relevant; the mechanism of action is documented at the molecular level; and the oral route of administration is compatible with standardized softgel capsule formulations titrated in linalool and linalyl acetate.

The duration of the trial (56 days) and the sample size represent the main limitations acknowledged by the authors. Questions remain open regarding different dosages, broader populations, and longer follow-up periods. Nevertheless, the direction indicated by the literature is sufficiently defined to guide informed formulation choices.

If your company is interested in developing formulations based on lavender essential oil: