How Compounds in Origanum majorana Affect Hormones, Oxidative Stress, and Ovarian Fertility
Polycystic ovary syndrome affects between 6 and 20% of women of childbearing age. It is one of the most common endocrine conditions and, at the same time, one of the least effectively managed: the conventional treatments available—from oral contraceptives to metformin—have significant limitations in terms of adverse effects and treatment adherence.
In this context, marjoram (Origanum majorana L.) has been used for centuries in traditional Mediterranean medicine for its effects on female hormonal imbalances. However, this empirical knowledge had not yet been supported by a rigorous molecular explanation.
A study published in BMC Complementary Medicine and Therapies in 2025 changed that. For the first time, researchers precisely mapped what happens in the body when marjoram compounds are ingested, using three distinct tools: serum metabolomic analysis, to track which molecules are actually absorbed; network pharmacology, to understand which proteins they interact with; molecular docking to simulate how they physically bind to their targets. The experimental model was PCOS induced with dehydroepiandrosterone (DHEA), an androgenic hormone that, at high doses, replicates the typical clinical picture of the syndrome.
Which compounds in marjoram actually enter the bloodstream?
Before understanding what marjoram does, it is important to know what is actually absorbed from it. Metabolomic analysis of serum answered this question: 25 compounds were identified in the blood of the treated animals, including molecules native to the plant and their derivatives. The structural classes include flavonoids, phenolic acids, fatty acids, lignans, and monoterpenes.
Among them all, two key players clearly stand out: apigenin and oleic acid. Apigenin is a flavonoid with phytoestrogenic properties, found in many plants, with a well-established body of research on its role in modulating hormonal and lipid profiles in PCOS. Oleic acid, the same monounsaturated fat found in olive oil, has shown positive effects on menstrual cycle regularity, ovulation, and insulin sensitivity.
The Numbers on Hormonal Modulation
How much does marjoram affect the hormonal profile? The data from the experimental model are clear. Induction of PCOS with DHEA resulted in a sharp drop in female hormones and an increase in testosterone. Oral administration of high-dose marjoram extract (100 mg/kg) significantly altered this profile:
- Progesterone: 1.30 to 13.00 ng/ml (value in the healthy group: 19.80 ng/ml)
- Estradiol: 40.00 to 270.35 pg/ml (value in the healthy group: 398.53 pg/ml)
- FSH (follicle-stimulating hormone): 7.16 to 30.10 ng/ml (value in the healthy group: 42.86 ng/ml)
- Testosterone: from 28.40 to 9.26 ng/ml, approaching the 5.70 ng/ml level of the healthy group
It is not a complete recovery, but the trend is clear. Among the proposed mechanisms,chlorogenic acid stimulates progesterone production by reducing LH (luteinizing hormone) and testosterone. Gallic acid appears to act on circulating androgens and adiponectin. Both compounds seem to influence the enzyme aromatase, which converts androgens into estrogens in the ovary—a key step in follicular maturation and the synthesis of estradiol.
Oxidative Stress: An Obstacle to Hormone Synthesis
There is another way in which PCOS affects the ovaries: oxidative stress. When free radicals exceed the body’s ability to neutralize them, ovarian hormone production is directly affected, impacting egg quality and hormone levels.
In the experimental model, DHEA produced exactly this: an excess of nitric oxide (NO)—a molecule that becomes toxic to tissues when present in excess—and a reduction in total antioxidant capacity (TAC). Oregano brought both parameters back to normal levels. This is not an isolated finding: people with low TAC levels also tend to have low estradiol levels. Fewer antioxidants available means less hormone is produced.
Among the compounds responsible for this action,rosmarinic acid stands out as the most potent free radical scavenger in the phytocomplex, working in synergy with the other flavonoids and phenolic acids present in the plant.
56 Target Genes: A Map of Molecular Interactions
Network pharmacology has made it possible to answer a broader question: With how many and which proteins do marjoram compounds interact in the body? The answer is 56 target genes, identified by cross-referencing absorbed metabolites with proteins associated with PCOS.
The most significant nodes in the network include CYP1B1 (the aromatase enzyme), TLR2 (an inflammatory response receptor), PPARG (a regulator of glucose and lipid metabolism), and HMGCR (a key enzyme in cholesterol biosynthesis). Analysis of biological pathways identified 34 pathways associated with PCOS, with steroid hormone biosynthesis ranking highest in importance: as many as 8 genes in the network are involved in this pathway, with very high statistical significance.
How molecules bind to protein targets
Molecular docking simulations have physically verified these interactions, confirming three particularly significant bonds:
- Caftaric acid → highest affinity for CYP1B1 (the aromatase enzyme): it binds to the active site through a direct bond with the enzyme’s metal center and multiple binding sites on the catalytic site
- Apigenin → optimal interaction with ESR2, the beta-estrogen receptor: the flavonoid’s planar structure fits perfectly into the binding pocket, partially mimicking the action of natural estradiol
- Dihydroisorhamnetin → greater affinity for MMP1, a metalloproteinase involved in ovarian tissue remodeling
The convergence of these data with evidence from network pharmacology confirms a coherent picture: marjoram does not act on a single target, but rather on a network of proteins that regulate steroidogenesis, inflammation, and hormonal metabolism.
What does this mean for supplement manufacturers?
The available evidence outlines a precise profile of use. To ensure the reproducibility of the observed effects, standardizing the extract for total flavonoids and phenolic acids—with a focus on apigenin and rosmarinic acid—is the essential quality benchmark.
The oral dosage form, containing a 70% ethanol extract, opens up real possibilities for use in capsules, tablets, or liquid formulations. Its compatibility with matrices rich in polyunsaturated fatty acids—as demonstrated by the synergistic effect of oleic and linoleic acids—suggests interesting formulation combinations for products designed to support women’s hormonal well-being.
If your company is interested in developing marjoram-based formulations
Source: Elfiky AM, Ibrahim RS, Khattab AR, Kadry MO, Ammar NM, Shawky E. “Exploring the therapeutic potential of marjoram (Origanum majorana L.) in polycystic ovary syndrome: insights from serum metabolomics, network pharmacology, and experimental validation.” BMC Complementary Medicine and Therapies. 2025;25:67. DOI: https://doi.org/10.1186/s12906-025-04774-5
