How the compounds of Origanum majorana act on 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 satisfactorily managed: the available conventional treatments, from oral contraceptives to metformin, show significant limitations in terms of adverse effects and therapeutic adherence.
In this context, marjoram (Origanum majorana L.) has occupied a place in traditional Mediterranean medicine for centuries for its effects on female hormonal imbalances. An empirical knowledge, however, that had not yet had a rigorous molecular explanation.
A study published in BMC Complementary Medicine and Therapies in 2025 changed this. For the first time, researchers precisely mapped what happens in the body when the compounds of marjoram are taken, using three distinct tools: serum metabolomics analysis, to trace 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 reproduces the typical picture of the syndrome.
Which marjoram compounds actually reach the bloodstream?
Before understanding what marjoram does, it is necessary to know what is actually absorbed. Serum metabolomics analysis answered this question: 25 compounds identified in the blood of treated animals, among original plant molecules and their derivatives. The structural classes include flavonoids, phenolic acids, fatty acids, lignans and monoterpenes.
Among all, two protagonists clearly emerge: apigenin and oleic acid. Apigenin is a flavonoid with phytoestrogenic properties, present in many vegetables, with a consolidated literature on the modulation of the hormonal and lipid profile in PCOS. Oleic acid, the same monounsaturated fat as olive oil, has shown positive effects on the regularity of the menstrual cycle, ovulation, and insulin sensitivity.
The numbers on hormonal modulation
How much does the hormonal profile change with marjoram? The data from the experimental model are clear. PCOS induction with DHEA produced a sharp drop in female hormones and an elevation of testosterone. Oral administration of high-dose marjoram extract (100 mg/kg) significantly modified this picture:
- Progesterone: from 1.30 to 13.00 ng/ml (value in the healthy group: 19.80 ng/ml)
- Estradiol: from 40.00 to 270.35 pg/ml (value in the healthy group: 398.53 pg/ml)
- FSH (follicle-stimulating hormone): from 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 of the healthy group
This is not a complete recovery, but the direction is clear. Among the hypothesized 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 appear to intervene on the aromatase enzyme, which in the ovary converts androgens to estrogens: a key step for follicular maturation and estradiol synthesis.
Oxidative stress: an obstacle to hormonal synthesis
There is another front on which PCOS weighs on the ovary: oxidative stress. When free radicals exceed the body’s ability to neutralize them, ovarian hormone production is directly affected, with effects on oocyte quality and hormone levels.
In the experimental model, DHEA produced exactly this: an excess of nitric oxide (NO), a molecule that in excess becomes toxic to tissues, and a reduction in total antioxidant capacity (TAC). Marjoram brought both parameters back toward normal. This is not an isolated finding: those with low TAC levels tend to also have low estradiol levels. Fewer antioxidants available, less hormone produced.
Among the compounds responsible for this action, rosmarinic acid emerges as the most powerful free radical scavenger in the phytocomplex, in synergy with the other flavonoids and phenolic acids present in the plant.
56 target genes: the map of molecular interactions
Network pharmacology allowed answering 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 the absorbed metabolites with the proteins associated with PCOS.
The most relevant nodes in the network include CYP1B1 (the aromatase enzyme), TLR2 (an inflammatory response receptor), PPARG (regulator of glucose and lipid metabolism), and HMGCR (key enzyme in cholesterol biosynthesis). Analysis of biological pathways identified 34 pathways correlated with PCOS, with steroid hormone biosynthesis at the top for relevance: as many as 8 genes from the network participate in it, with very high statistical significance.
How the molecules bind to protein targets
Molecular docking simulations physically verified these interactions, confirming three particularly relevant bonds:
- Caftaric acid → maximum affinity toward CYP1B1 (the aromatase enzyme): it inserts into the active site through a direct bond with the metallic center of the enzyme and multiple anchor points at the catalytic site
- Apigenin → optimal interaction with ESR2, the estrogen receptor beta: the planar structure of the flavonoid perfectly adapts to the binding pocket, partially mimicking the action of natural estradiol
- Dihydroisorhamnetin → greater affinity toward MMP1, a metalloprotease involved in ovarian tissue remodeling
The convergence of these data with the evidence from network pharmacology confirms a coherent picture: marjoram does not act on a single target, but on a network of proteins governing steroidogenesis, inflammation, and hormonal metabolism.
What this means for supplement formulators
The available evidence outlines a precise application profile. To ensure the reproducibility of observed effects, standardization of the extract in total flavonoids and phenolic acids, with attention to apigenin and rosmarinic acid, represents the essential quality reference.
The oral delivery format, with 70% ethanolic extract, opens concrete possibilities in capsules, tablets, or liquid formats. Compatibility with matrices rich in polyunsaturated fatty acids, documented by the synergistic contribution of oleic and linoleic acid, suggests interesting formulation combinations for products dedicated to female hormonal wellness.
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
