The science behind how it can help you navigate this transition, and what to look out for when choosing a supplement
Nobody warns you that the mood symptoms of perimenopause are the first to show up, long before the stereotypical hot flushes and night sweats This symptom timeline is confirmed in the research (1).
Perimenopause typically starts in your mid 30’s to late 40’s, and it comes with intense mood changes: irritability, mood crashes, feeling overwhelmed, foggy, and not quite yourself (2).
The message, spoken or not: “this is just something you go through with age”. It’s brushed off, and you’re left to navigate one of the most destabilising periods of life without proper support.
But there are evidence-based options to help you through this period that are not widely known. What's happening in your brain during perimenopause is specific, measurable, and increasingly well understood. And there's growing evidence that saffron extract, and the bioactive compounds inside it, can meaningfully support mood during this transition.
Here's the science behind why.
In Perimenopause, Your Brain's Mood Chemistry is Changing
Perimenopause isn't a single hormonal event, it's years of erratic fluctuations before estrogen and progesterone finally settle at their lower postmenopausal levels. And estrogen does far more than regulate your cycle.
In a normally functioning brain, estrogen plays an active role in your serotonin system, which is the network of brain chemistry most closely tied to mood, emotional resilience, and the ability to cope with stress.
Normally, estrogen can (3):
◉ Regulate serotonin synthesis: estrogen boosts the production of the enzyme that can produce serotonin AND reduces the levels of the enzyme that can destroy it
◉ Inhibit serotonin reuptake: Estrogen can inhibit the gene responsible for the serotonin reuptake transporter (SERT), increasing the amount of available serotonin in the synapse
◉ Modulate serotonin receptors: estrogen controls which serotonin receptors are expressed in the synapse
During perimenopause, these levels of estrogen decline, removing the protective effects on the serotonergic system, meaning (3):
1. Decreased serotonin production
2. Accelerated serotonin breakdown and removal
3. Imbalance in serotonin receptors → more 5-HT2 receptors which means disrupted signalling!
This lack of serotonin can trigger depressive episodes, cognitive difficulties and poor concentration (brain fog), and inability to cope with stress.
What Saffron Extract Actually Does in the Brain
Saffron contains two active compounds, crocin and safranal, that are shown to act on the serotonin system through mechanisms that parallel those of antidepressant medication, but with some important differences (4,5).
Like SSRIs, crocin and safranal inhibit serotonin reuptake, keeping it available in the synapse to bind to postsynaptic receptors and produce its mood-stabilising effect. But saffron extract goes further: crocin also inhibits monoamine oxidase, the enzyme responsible for breaking serotonin down. This dual action, blocking both removal and degradation, means saffron is working on the serotonin system through two pathways simultaneously.
In head-to-head clinical trials, saffron extract has performed comparably to SSRIs in reducing depression symptoms, but with significantly fewer adverse effects (meta-analysis of 8 studies) (6). It also performs significantly better than a placebo, indicating these effects are real (meta-analysis of 12 studies)(7) .
The mechanisms through which saffron supports mood are multifactorial and that the serotonergic pathway, while primary, may not be the only one at work. Saffron also inhibits the reuptake of dopamine and noradrenaline, two neurotransmitters closely tied to motivation, energy, and the capacity for pleasure. For someone navigating perimenopausal fatigue and emotional flatness, this broader action across multiple systems matters.
What the Research Shows for Perimenopausal Women Specifically
In a 12-week randomised controlled trial, 86 perimenopausal women aged 40 to 60 received either a placebo or 28mg of saffron extract daily. The results (8):
The saffron group experienced a significant reduction in mood symptoms compared to placebo: a 33% reduction in anxiety and a 32% reduction in depression. Negative affect - including feelings of stress, hostility, and nervousness - was significantly lower in the saffron group.
Why a Standardised Extract Matters
Saffron extract is available in supplements, but they are not all equal. The active compounds responsible for saffron's neurological effects, crocin and safranal, are present in highly variable concentrations in the culinary saffron spice, and in most generic supplements. Without standardisation, you have no way of knowing whether you're getting a therapeutic dose.
A quality saffron supplement should be extracted from the red stigma, and importantly - standardised to contain at least 3.5% of these bioactive compounds. DITTO exceeds this, at 6.56% and contains the 30mg dose shown to be effective in clinical trials.
A note if you’re also struggling with ADHD or PMDD
Perimenopause can also bring along a devastating exacerbation of ADHD or PMDD, and we hear all the time from our community how life altering this is. Interestingly, saffron extract has been studied in these populations too. In PMDD, saffron extract has been shown to outperform placebo and be comparable to fluoxetine (an antidepressant) in improving PMDD symptoms (9). In those with ADHD, saffron extract was seen to be effective on its own and as an additive to ADHD medication (10).
The Takeaway
Perimenopausal mood symptoms are not a character flaw or an overreaction. They are the downstream consequence of a specific neurochemical disruption, one that is increasingly well documented and, importantly, increasingly addressable.
Saffron extract, at the right dose and standardisation, targets the serotonin system in a way that is both mechanistically coherent and clinically supported. For the emotional dimension of this transition, the anxiety, the low mood, the sense of losing yourself, the evidence is real, and it's growing.
If you've been left without support, or you’re searching for something natural to help you navigate the mood changes that come with perimenopause, this is worth knowing about.
References:
1. Thurston, R.C., Thomas, H.N., Castle, A.J. et al. Menopause as a biological and psychological transition. Nat Rev Psychol 4, 530–543 (2025). https://doi.org/10.1038/s44159-025-00463-9
2. Cunningham AC, Hewings-Martin Y, Wickham AP, et al. Perimenopause symptoms, severity, and healthcare seeking in women in the US. npj Womens Health 3, 12 (2025). https://doi.org/10.1038/s44294-025-00061-3
3. Turek, J., & Gąsior, Ł. (2023). Estrogen fluctuations during the menopausal transition are a risk factor for depressive disorders. Pharmacological reports : PR, 75(1), 32–43. https://doi.org/10.1007/s43440-022-00444-2
4. Lopresti A. L., and Drummond P. D. (2014), Saffron (Crocus sativus) for depression: a systematic review of clinical studies and examination of underlying antidepressant mechanisms of action, Hum. Psychopharmacol Clin Exp, 29, 517–527, doi: 10.1002/hup.2434
5. Siddiqui SA, Ali Redha A, Snoeck ER, Singh S, Simal-Gandara J, Ibrahim SA, Jafari SM. Anti-Depressant Properties of Crocin Molecules in Saffron. Molecules. 2022 Mar 23;27(7):2076. doi: 10.3390/molecules27072076. PMID: 35408474; PMCID: PMC9000812.
6. Shafiee A, Jafarabady K, Seighali N, Mohammadi I, Rajai Firouz Abadi S, Abhari FS, Bakhtiyari M. Effect of Saffron Versus Selective Serotonin Reuptake Inhibitors (SSRIs) in Treatment of Depression and Anxiety: A Meta-analysis of Randomized Controlled Trials. Nutr Rev. 2025 Mar 1;83(3):e751-e761. doi: 10.1093/nutrit/nuae076. PMID: 38913392.
7. Dai L, Chen L, Wang W. Safety and Efficacy of Saffron (Crocus sativus L.) for Treating Mild to Moderate Depression: A Systematic Review and Meta-analysis. J Nerv Ment Dis. 2020 Apr;208(4):269-276.
8. Lopresti, A. L., & Smith, S. J. (2021). The Effects of a Saffron Extract (affron®) on Menopausal Symptoms in Women during Perimenopause: A Randomised, Double-Blind, Placebo-Controlled Study. Journal of menopausal medicine, 27(2), 66–78. https://doi.org/10.6118/jmm.21002
9. Rajabi F, Rahimi M, Sharbafchizadeh MR, Tarrahi MJ. Saffron for the Management of Premenstrual Dysphoric Disorder: A Randomized Controlled Trial. Adv Biomed Res. 2020
10. Pazoki B, Zandi N, Assaf Z, Moghaddam HS, Zeinoddini A, Mohammadi MR, et al. Efficacy and safety of saffron as adjunctive therapy in adults with attention-deficit/hyperactivity disorder: A randomized, double-blind, placebo-controlled clinical trial. Advances in Integrative Medicine. 2022
